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Burkard M, Piotrowsky A, Leischner C, Detert K, Venturelli S, Marongiu L. The Antiviral Activity of Polyphenols. Mol Nutr Food Res 2025:e70042. [PMID: 40166854 DOI: 10.1002/mnfr.70042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 02/27/2025] [Accepted: 03/10/2025] [Indexed: 04/02/2025]
Abstract
Polyphenols are secondary metabolites produced by a large variety of plants. These compounds that comprise the class of phenolic acids, stilbenes, lignans, coumarins, flavonoids, and tannins have a wide range of employment, from food production to medical usages. Among the beneficial applications of polyphenols, their antiviral activity is gaining importance due to the increased prevalence of drug-resistant viruses such as herpes and hepatitis B viruses. In the present review, we provide an overview of the most promising or commonly used antiviral polyphenols and their mechanisms of action focusing on their effects on enveloped viruses of clinical importance (double-stranded linear or partially double-stranded circular DNA viruses, negative sense single-stranded RNA viruses with nonsegmented or segmented genomes, and positive sense single-stranded RNA viruses). The present work emphasizes the relevance of polyphenols, in particular epigallocatechin-3-gallate and resveratrol, as alternative or supportive antivirals. Polyphenols could interfere with virtually all steps of viral infection, from the adsorption to the release of viral particles. The activity of polyphenols against viruses is especially relevant given the risk of widespread outbreaks associated with viruses, remarked by the recent COVID-19 pandemic.
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Affiliation(s)
- Markus Burkard
- Department of Nutritional Biochemistry, University of Hohenheim, Stuttgart, Germany
| | - Alban Piotrowsky
- Department of Nutritional Biochemistry, University of Hohenheim, Stuttgart, Germany
| | - Christian Leischner
- Department of Nutritional Biochemistry, University of Hohenheim, Stuttgart, Germany
| | - Katja Detert
- Department of Nutritional Biochemistry, University of Hohenheim, Stuttgart, Germany
| | - Sascha Venturelli
- Department of Nutritional Biochemistry, University of Hohenheim, Stuttgart, Germany
- Department of Vegetative and Clinical Physiology, Institute of Physiology, University of Tuebingen, Tuebingen, Germany
| | - Luigi Marongiu
- Department of Nutritional Biochemistry, University of Hohenheim, Stuttgart, Germany
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Ayed A. The role of natural products versus miRNA in renal cell carcinoma: implications for disease mechanisms and diagnostic markers. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:6417-6437. [PMID: 38691151 DOI: 10.1007/s00210-024-03121-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 04/24/2024] [Indexed: 05/03/2024]
Abstract
Natural products are chemical compounds produced by living organisms. They are isolated and purified to determine their function and can potentially be used as therapeutic agents. The ability of some bioactive natural products to modify the course of cancer is fascinating and promising. In the past 50 years, there have been advancements in cancer therapy that have increased survival rates for localized tumors. However, there has been little progress in treating advanced renal cell carcinoma (RCC), which is resistant to radiation and chemotherapy. Oncogenes and tumor suppressors are two roles played by microRNAs (miRNAs). They are involved in important pathogenetic mechanisms like hypoxia and epithelial-mesenchymal transition (EMT); they control apoptosis, cell growth, migration, invasion, angiogenesis, and proliferation through target proteins involved in various signaling pathways. Depending on their expression pattern, miRNAs may identify certain subtypes of RCC or distinguish tumor tissue from healthy renal tissue. As diagnostic biomarkers of RCC, circulating miRNAs show promise. There is a correlation between the expression patterns of several miRNAs and the prognosis and diagnosis of patients with RCC. Potentially high-risk primary tumors may be identified by comparing original tumor tissue with metastases. Variations in miRNA expression between treatment-sensitive and therapy-resistant patients' tissues and serum allow for the estimation of responsiveness to target therapy. Our knowledge of miRNAs' function in RCC etiology has a tremendous uptick. Finding and validating their gene targets could have an immediate effect on creating anticancer treatments based on miRNAs. Several miRNAs have the potential to be used as biomarkers for diagnosis and prognosis. This review provides an in-depth analysis of the current knowledge regarding natural compounds and their modes of action in combating cancer. Also, this study aims to give information about the diagnostic and prognostic value of miRNAs as cancer biomarkers and their involvement in the pathogenesis of RCC.
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Affiliation(s)
- Abdullah Ayed
- Department of Surgery, College of Medicine, University of Bisha, P.O Box 551, 61922, Bisha, Saudi Arabia.
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Bedoya-Agudelo JP, López-Carvajal JE, Quiguanás-Guarín ES, Cardona N, Padilla-Sanabria L, Castaño-Osorio JC. Assessment of Antimicrobial and Cytotoxic Activities of Liposomes Loaded with Curcumin and Lippia origanoides Essential Oil. Biomolecules 2024; 14:851. [PMID: 39062565 PMCID: PMC11275147 DOI: 10.3390/biom14070851] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 07/08/2024] [Accepted: 07/09/2024] [Indexed: 07/28/2024] Open
Abstract
(1) Introduction: Curcumin and Lippia origanoides essential oils have a broad spectrum of biological activities; however, their physicochemical instability, low solubility, and high volatility limit their therapeutic use. Encapsulation in liposomes has been reported as a feasible approach to increase the physicochemical stability of active substances, protect them from interactions with the environment, modulate their release, reduce their volatility, improve their bioactivity, and reduce their toxicity. To date, there are no reports on the co-encapsulation of curcumin and Lippia origanoides essential oils in liposomes. Therefore, the objective of this work is to prepare and physiochemical characterize liposomes loaded with the mixture of these compounds and to evaluate different in vitro biological activities. (2) Methods: Liposomes were produced using the thin-layer method and physiochemical characteristics were calculated. The antimicrobial and cytotoxic activities of both encapsulated and non-encapsulated compounds were evaluated. (3) Results: Empty and loaded nanometric-sized liposomes were obtained that are monodisperse and have a negative zeta potential. They inhibited the growth of Staphylococcus aureus and did not exhibit cytotoxic activity against mammalian cells. (4) Conclusions: Encapsulation in liposomes was demonstrated to be a promising strategy for natural compounds possessing antimicrobial activity.
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Affiliation(s)
- Juan Pablo Bedoya-Agudelo
- Molecular Immunology Group (GYMOL), Center of Biomedical Research, Faculty of Health Sciences, Quindío University, Armenia 630003, Colombia; (J.P.B.-A.); (J.E.L.-C.); (E.S.Q.-G.); (J.C.C.-O.)
| | - Jhon Esteban López-Carvajal
- Molecular Immunology Group (GYMOL), Center of Biomedical Research, Faculty of Health Sciences, Quindío University, Armenia 630003, Colombia; (J.P.B.-A.); (J.E.L.-C.); (E.S.Q.-G.); (J.C.C.-O.)
| | - Edwin Stiven Quiguanás-Guarín
- Molecular Immunology Group (GYMOL), Center of Biomedical Research, Faculty of Health Sciences, Quindío University, Armenia 630003, Colombia; (J.P.B.-A.); (J.E.L.-C.); (E.S.Q.-G.); (J.C.C.-O.)
| | - Nestor Cardona
- Group of Investigation in Oral Health, Faculty of Dentistry, Antonio Nariño University, Armenia 630001, Colombia;
| | - Leonardo Padilla-Sanabria
- Molecular Immunology Group (GYMOL), Center of Biomedical Research, Faculty of Health Sciences, Quindío University, Armenia 630003, Colombia; (J.P.B.-A.); (J.E.L.-C.); (E.S.Q.-G.); (J.C.C.-O.)
| | - Jhon Carlos Castaño-Osorio
- Molecular Immunology Group (GYMOL), Center of Biomedical Research, Faculty of Health Sciences, Quindío University, Armenia 630003, Colombia; (J.P.B.-A.); (J.E.L.-C.); (E.S.Q.-G.); (J.C.C.-O.)
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Chen Y, Li Y, Lu L, Zou P. Zafirlukast, as a viral inactivator, potently inhibits infection of several flaviviruses, including Zika virus, dengue virus, and yellow fever virus. Antimicrob Agents Chemother 2024; 68:e0016824. [PMID: 38809067 PMCID: PMC11232407 DOI: 10.1128/aac.00168-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 05/02/2024] [Indexed: 05/30/2024] Open
Abstract
Zika virus (ZIKV) is one of the mosquito-borne flaviviruses that exhibits a unique tropism to nervous systems and is associated with Guillain-Barre syndrome and congenital Zika syndrome (CZS). Dengue virus (DENV) and yellow fever virus (YFV), the other two mosquito-borne flaviviruses, have also been circulating for a long time and cause severe diseases, such as dengue hemorrhagic fever and yellow fever, respectively. However, there are no safe and effective antiviral drugs approved for the treatment of infections or coinfections of these flaviviruses. Here, we found that zafirlukast, a pregnancy-safe leukotriene receptor antagonist, exhibited potent antiviral activity against infections of ZIKV strains from different lineages in different cell lines, as well as against infections of DENV-2 and YFV 17D. Mechanistic studies demonstrated that zafirlukast directly and irreversibly inactivated these flaviviruses by disrupting the integrity of the virions, leading to the loss of viral infectivity, hence inhibiting the entry step of virus infection. Considering its efficacy against flaviviruses, its safety for pregnant women, and its neuroprotective effect, zafirlukast is a promising candidate for prophylaxis and treatment of infections or coinfections of ZIKV, DENV, and YFV, even in pregnant women.
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Affiliation(s)
- Yongkang Chen
- Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Yuan Li
- Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Lu Lu
- Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Peng Zou
- Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Fudan University, Shanghai, China
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Kombe Kombe AJ, Fotoohabadi L, Nanduri R, Gerasimova Y, Daskou M, Gain C, Sharma E, Wong M, Kelesidis T. The Role of the Nrf2 Pathway in Airway Tissue Damage Due to Viral Respiratory Infections. Int J Mol Sci 2024; 25:7042. [PMID: 39000157 PMCID: PMC11241721 DOI: 10.3390/ijms25137042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 06/14/2024] [Accepted: 06/20/2024] [Indexed: 07/16/2024] Open
Abstract
Respiratory viruses constitute a significant cause of illness and death worldwide. Respiratory virus-associated injuries include oxidative stress, ferroptosis, inflammation, pyroptosis, apoptosis, fibrosis, autoimmunity, and vascular injury. Several studies have demonstrated the involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2) in the pathophysiology of viral infection and associated complications. It has thus emerged as a pivotal player in cellular defense mechanisms against such damage. Here, we discuss the impact of Nrf2 activation on airway injuries induced by respiratory viruses, including viruses, coronaviruses, rhinoviruses, and respiratory syncytial viruses. The inhibition or deregulation of Nrf2 pathway activation induces airway tissue damage in the presence of viral respiratory infections. In contrast, Nrf2 pathway activation demonstrates protection against tissue and organ injuries. Clinical trials involving Nrf2 agonists are needed to define the effect of Nrf2 therapeutics on airway tissues and organs damaged by viral respiratory infections.
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Affiliation(s)
- Arnaud John Kombe Kombe
- Division of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; (A.J.K.K.)
| | - Leila Fotoohabadi
- Division of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; (A.J.K.K.)
| | - Ravikanth Nanduri
- Division of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; (A.J.K.K.)
| | - Yulia Gerasimova
- Division of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; (A.J.K.K.)
| | - Maria Daskou
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Chandrima Gain
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Eashan Sharma
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Michael Wong
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Theodoros Kelesidis
- Division of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; (A.J.K.K.)
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
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Azarkar S, Abedi M, Lavasani ASO, Ammameh AH, Goharipanah F, Baloochi K, Bakhshi H, Jafari A. Curcumin as a natural potential drug candidate against important zoonotic viruses and prions: A narrative review. Phytother Res 2024; 38:3080-3121. [PMID: 38613154 DOI: 10.1002/ptr.8119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 12/09/2023] [Accepted: 12/17/2023] [Indexed: 04/14/2024]
Abstract
Zoonotic diseases are major public health concerns and undeniable threats to human health. Among Zoonotic diseases, zoonotic viruses and prions are much more difficult to eradicate, as they result in higher infections and mortality rates. Several investigations have shown curcumin, the active ingredient of turmeric, to have wide spectrum properties such as anti-microbial, anti-vascular, anti-inflammatory, anti-tumor, anti-neoplastic, anti-oxidant, and immune system modulator properties. In the present study, we performed a comprehensive review of existing in silico, in vitro, and in vivo evidence on the antiviral (54 important zoonotic viruses) and anti-prion properties of curcumin and curcuminoids in PubMed, Google Scholar, Science Direct, Scopus, and Web of Science databases. Database searches yielded 13,380 results, out of which 216 studies were eligible according to inclusion criteria. Of 216 studies, 135 (62.5%), 24 (11.1%), and 19 (8.8%) were conducted on the effect of curcumin and curcuminoids against SARS-CoV-2, Influenza A virus, and dengue virus, respectively. This review suggests curcumin and curcuminoids as promising therapeutic agents against a wide range of viral zoonoses by targeting different proteins and signaling pathways.
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Affiliation(s)
- Setareh Azarkar
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Masoud Abedi
- Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
| | | | | | - Fatemeh Goharipanah
- Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
| | - Kimiya Baloochi
- Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
| | - Hasan Bakhshi
- Vector-Borne Diseases Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Amirsajad Jafari
- Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
- Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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Adeosun WB, Loots DT. Medicinal Plants against Viral Infections: A Review of Metabolomics Evidence for the Antiviral Properties and Potentials in Plant Sources. Viruses 2024; 16:218. [PMID: 38399995 PMCID: PMC10892737 DOI: 10.3390/v16020218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 01/22/2024] [Accepted: 01/29/2024] [Indexed: 02/25/2024] Open
Abstract
Most plants have developed unique mechanisms to cope with harsh environmental conditions to compensate for their lack of mobility. A key part of their coping mechanisms is the synthesis of secondary metabolites. In addition to their role in plants' defense against pathogens, they also possess therapeutic properties against diseases, and their use by humans predates written history. Viruses are a unique class of submicroscopic agents, incapable of independent existence outside a living host. Pathogenic viruses continue to pose a significant threat to global health, leading to innumerable fatalities on a yearly basis. The use of medicinal plants as a natural source of antiviral agents has been widely reported in literature in the past decades. Metabolomics is a powerful research tool for the identification of plant metabolites with antiviral potentials. It can be used to isolate compounds with antiviral capacities in plants and study the biosynthetic pathways involved in viral disease progression. This review discusses the use of medicinal plants as antiviral agents, with a special focus on the metabolomics evidence supporting their efficacy. Suggestions are made for the optimization of various metabolomics methods of characterizing the bioactive compounds in plants and subsequently understanding the mechanisms of their operation.
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Affiliation(s)
- Wilson Bamise Adeosun
- Human Metabolomics, North-West University, Private Bag X6001, Box 269, Potchefstroom 2531, South Africa;
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Nittayananta W, Lerdsamran H, Chutiwitoonchai N, Promsong A, Srichana T, Netsomboon K, Prasertsopon J, Kerdto J. A novel film spray containing curcumin inhibits SARS-CoV-2 and influenza virus infection and enhances mucosal immunity. Virol J 2024; 21:26. [PMID: 38263162 PMCID: PMC10807123 DOI: 10.1186/s12985-023-02282-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 12/29/2023] [Indexed: 01/25/2024] Open
Abstract
BACKGROUND Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and influenza virus is still a major worldwide health concern. Plants are a good source of bioactive compounds to be used as preventive measures for both inhibiting the virus binding and enhancing mucosal innate immunity. Curcumin has been shown to possess antiviral activity and modulate innate immunity. Therefore, the purpose of this study was to develop an oro-nasal film spray containing curcumin and determine its antiviral activity against SARS-CoV-2 and influenza virus infection, as well as its effects on mucosal innate immunity and inflammatory cytokines in vitro. METHODS The antiviral activity of the film spray against SARS-CoV-2, influenza A/H1N1, A/H3N2, and influenza B was assessed in vitro by plaque reduction assay. Cytotoxicity of the film spray to oral keratinocytes and nasal epithelial cells was assessed by MTT assay, and cytotoxicity to Vero and MDCK cells was assessed by an MTS-based cytotoxicity assay. Oral and nasal innate immune markers in response to the film spray were determined by ELISA and by a commercial Milliplex Map Kit, respectively. RESULTS Our data show that the film spray containing curcumin can inhibit both SARS-CoV-2 and influenza virus infections while maintaining cell viability. Results obtained among 4 viruses revealed that curcumin film spray demonstrated the highest inhibitory activity against SARS-CoV-2 with the lowest EC50 of 3.15 µg/ml and the highest SI value of 4.62, followed by influenza B (EC50 = 6.32 µg/ml, SI = 2.04), influenza A/H1N1 (EC50 = 7.24 µg/ml, SI = 1.78), and influenza A/H3N2 (EC50 > 12.5 µg/ml, SI < 1.03), respectively. Antimicrobial peptides LL-37 and HD-5, IL-6 and TNF-α produced by oral keratinocytes were significantly induced by the film spray, while hBD2 was significantly reduced. CONCLUSION Film spray containing curcumin possesses multiple actions against SARS-CoV-2 infection by inhibiting ACE-2 binding in target cells and enhancing mucosal innate immunity. The film spray can also inhibit influenza virus infection. Therefore, the curcumin film spray may be effective in preventing the viral infection of both SARS-CoV-2 and influenza.
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Affiliation(s)
| | - Hatairat Lerdsamran
- Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand
| | - Nopporn Chutiwitoonchai
- National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand
| | - Aornrutai Promsong
- Faculty of Medicine, Princess of Naradhiwas University, Narathiwat, Thailand
| | - Teerapol Srichana
- Drug Delivery System Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, Thailand
- Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, Thailand
| | | | - Jarunee Prasertsopon
- Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand
| | - Jaruta Kerdto
- Thammasat Hospital, Thammasat University, Pathum Thani, Thailand
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Daskou M, Fotooh Abadi L, Gain C, Wong M, Sharma E, Kombe Kombe AJ, Nanduri R, Kelesidis T. The Role of the NRF2 Pathway in the Pathogenesis of Viral Respiratory Infections. Pathogens 2023; 13:39. [PMID: 38251346 PMCID: PMC10819673 DOI: 10.3390/pathogens13010039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 12/27/2023] [Accepted: 12/28/2023] [Indexed: 01/23/2024] Open
Abstract
In humans, acute and chronic respiratory infections caused by viruses are associated with considerable morbidity and mortality. Respiratory viruses infect airway epithelial cells and induce oxidative stress, yet the exact pathogenesis remains unclear. Oxidative stress activates the transcription factor NRF2, which plays a key role in alleviating redox-induced cellular injury. The transcriptional activation of NRF2 has been reported to affect both viral replication and associated inflammation pathways. There is complex bidirectional crosstalk between virus replication and the NRF2 pathway because virus replication directly or indirectly regulates NRF2 expression, and NRF2 activation can reversely hamper viral replication and viral spread across cells and tissues. In this review, we discuss the complex role of the NRF2 pathway in the regulation of the pathogenesis of the main respiratory viruses, including coronaviruses, influenza viruses, respiratory syncytial virus (RSV), and rhinoviruses. We also summarize the scientific evidence regarding the effects of the known NRF2 agonists that can be utilized to alter the NRF2 pathway.
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Affiliation(s)
- Maria Daskou
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Leila Fotooh Abadi
- Department of Internal Medicine, Division of Infectious Diseases and Geographic Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; (L.F.A.); (R.N.)
| | - Chandrima Gain
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Michael Wong
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Eashan Sharma
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Arnaud John Kombe Kombe
- Department of Internal Medicine, Division of Infectious Diseases and Geographic Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; (L.F.A.); (R.N.)
| | - Ravikanth Nanduri
- Department of Internal Medicine, Division of Infectious Diseases and Geographic Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; (L.F.A.); (R.N.)
| | - Theodoros Kelesidis
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
- Department of Internal Medicine, Division of Infectious Diseases and Geographic Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; (L.F.A.); (R.N.)
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10
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Wu YQ, Tong T. Curcumae Rhizoma: A botanical drug against infectious diseases. Front Pharmacol 2023; 13:1015098. [PMID: 36703758 PMCID: PMC9871392 DOI: 10.3389/fphar.2022.1015098] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 12/22/2022] [Indexed: 01/11/2023] Open
Abstract
Curcumae Rhizoma is the dry rhizome coming from Curcuma longa L. which grow widely in tropical south and southwest Asia. It has been used to treat conditions such as dermatoses, infections, stress, and depression. Moreover, in China, Curcumae Rhizoma and its active constituents have been made into different pharmaceutical preparations. Growing evidence suggests that these preparations can exert antioxidant, anti-inflammatory, and anti-cancer effects, which may play crucial roles in the treatment of various diseases, including cancer, infectious-, autoimmune-, neurological-, and cardiovascular diseases, as well as diabetes. The anti-infective effect of Curcumae Rhizoma has become a popular field of research around the world, including for the treatment of COVID-19, influenza virus, hepatitis B virus, human immunodeficiency virus, and human papilloma virus, among others. In this paper, the basic characteristics of Curcumae Rhizoma and its active constituents are briefly introduced, and we also give an overview on their applications and mechanisms in infectious diseases.
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COVID-19: Reducing the risk via diet and lifestyle. JOURNAL OF INTEGRATIVE MEDICINE 2023; 21:1-16. [PMID: 36333177 PMCID: PMC9550279 DOI: 10.1016/j.joim.2022.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 07/15/2022] [Indexed: 01/17/2023]
Abstract
This review shows that relatively simple changes to diet and lifestyle can significantly, and rapidly, reduce the risks associated with coronavirus disease 2019 (COVID-19) in terms of infection risk, severity of disease, and even disease-related mortality. A wide range of interventions including regular exercise, adequate sleep, plant-based diets, maintenance of healthy weight, dietary supplementation, and time in nature have each been shown to have beneficial effects for supporting more positive health outcomes with COVID-19, in addition to promoting better overall health. This paper brings together literature from these areas and presents the argument that non-pharmaceutical approaches should not be overlooked in our response to COVID-19. It is noted that, in several cases, interventions discussed result in risk reductions equivalent to, or even greater than, those associated with currently available vaccines. Where the balance of evidence suggests benefits, and the risk is minimal to none, it is suggested that communicating the power of individual actions to the public becomes morally imperative. Further, many lives could be saved, and many harms from the vaccine mandates avoided, if we were willing to embrace this lifestyle-centred approach in our efforts to deal with COVID-19.
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Yadav PK, Jaiswal A, Singh RK. In silico study on spice-derived antiviral phytochemicals against SARS-CoV-2 TMPRSS2 target. J Biomol Struct Dyn 2022; 40:11874-11884. [PMID: 34427179 DOI: 10.1080/07391102.2021.1965658] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Corona Virus Disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a pandemic that has claimed so far over half a million human life across the globe. Researchers all over the world are exploring various molecules including phytochemicals to get a potential anti-COVID-19 drug. Certain phytochemicals present in some spices are claimed to possess antiviral, anti-bacterial, and anti-fungal properties. Hence, an in-silico study was done by selecting eighteen well reported antiviral phytochemicals from some spices commonly used in Indian kitchen viz. Curcuma longa (Turmeric), Nigella sativa (Black cumin), Piper nigrum (Black pepper), Trachyspermum ammi (Carom) and Zingiber officinale (Ginger) to find out whether they can prevent SARS-CoV-2 infection. Firstly, we predicted the structure of TMPRSS2 (transmembrane protease serine 2), a host protein that truncates spike protein of SARS-CoV-2 thereby facilitating its endocytosis, and then docked against its catalytic domain the selected phytochemicals and camostat (a well-known synthetic inhibitor of TMPRSS2). Thereafter, stability of seven best docked phytochemicals and camostat were scrutinized by Molecular Dynamic Simulation (MDS). MDS analysis indicated bisdemethoxycurcumin (BDMC), carvacrol and thymol as better inhibitors than the camostat due to their stable binding with TMPRSS2 in its oxyanion hole and inducing subtle modification in the spatial arrangement of the catalytic triad residues. Among these three phytochemicals, carvacrol appeared to be the best inhibitor, followed by BDMC, whereas thymol was least effective.
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Affiliation(s)
- Pradeep Kumar Yadav
- Bioinformatics Centre, Faculty of Life Sciences, Rajiv Gandhi University, Doimukh, Arunachal Pradesh, India
| | - Amit Jaiswal
- Bioinformatics Centre, Faculty of Life Sciences, Rajiv Gandhi University, Doimukh, Arunachal Pradesh, India
| | - Rajiv Kumar Singh
- Bioinformatics Centre, Faculty of Life Sciences, Rajiv Gandhi University, Doimukh, Arunachal Pradesh, India
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13
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Park S, Kim JY, Kwon HC, Jang DS, Song YJ. Antiviral Activities of Ethyl Pheophorbides a and b Isolated from Aster pseudoglehnii against Influenza Viruses. Molecules 2022; 28:41. [PMID: 36615236 PMCID: PMC9822050 DOI: 10.3390/molecules28010041] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 12/15/2022] [Accepted: 12/17/2022] [Indexed: 12/24/2022] Open
Abstract
Screening of the antiviral and virucidal activities of ethanol extracts from plants endemic to the Republic of Korea revealed the inhibitory activity of a 70% ethanol extract of the whole plant of A. pseudoglehnii (APE) against influenza virus infection. Two chlorophyll derivatives, ethyl pheophorbides a and b, isolated as active components of APE, exerted virucidal effects with no evident cytotoxicity. These compounds were effective only under conditions of direct incubation with the virus, and exerted no effects on the influenza A virus (IAV) surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). Interestingly, virucidal activities of ethyl pheophorbides a and b were observed against enveloped but not non-enveloped viruses, suggesting that these compounds act by affecting the integrity of the viral membrane and reducing infectivity.
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Affiliation(s)
- Subin Park
- Department of Life Science, Gachon University, Seongnam 13120, Republic of Korea
| | - Ji-Young Kim
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Hak Cheol Kwon
- Natural Product Informatics Research Center, Korea Institute of Science and Technology (KIST), Gangneung Institute, Gangneung 25451, Republic of Korea
| | - Dae Sik Jang
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Yoon-Jae Song
- Department of Life Science, Gachon University, Seongnam 13120, Republic of Korea
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14
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Ranjbar M, Rahimi A, Baghernejadan Z, Ghorbani A, Khorramdelazad H. Role of CCL2/CCR2 axis in the pathogenesis of COVID-19 and possible Treatments: All options on the Table. Int Immunopharmacol 2022; 113:109325. [PMID: 36252475 PMCID: PMC9561120 DOI: 10.1016/j.intimp.2022.109325] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 10/05/2022] [Accepted: 10/05/2022] [Indexed: 11/05/2022]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is cause of the novel coronavirus disease (COVID-19). In the last two years, SARS-CoV-2 has infected millions of people worldwide with different waves, resulting in the death of many individuals. The evidence disclosed that the host immune responses to SARS-CoV-2 play a pivotal role in COVID-19 pathogenesis and clinical manifestations. In addition to inducing antiviral immune responses, SARS-CoV-2 can also cause dysregulated inflammatory responses characterized by the noticeable release of proinflammatory mediators in COVID-19 patients. Among these proinflammatory mediators, chemokines are considered a subset of cytokines that participate in the chemotaxis process to recruit immune and non-immune cells to the site of inflammation and infection. Researchers have demonstrated that monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor (CCR2) are involved in the recruitment of monocytes and infiltration of these cells into the lungs of patients suffering from COVID-19. Moreover, elevated levels of CCL2 have been reported in the bronchoalveolar lavage fluid (BALF) obtained from patients with severe COVID-19, initiating cytokine storm and promoting CD163+ myeloid cells infiltration in the airways and further alveolar damage. Therefore, CCL2/CCR axis plays a key role in the immunopathogenesis of COVID-19 and targeted therapy of involved molecules in this axis can be a potential therapeutic approach for these patients. This review discusses the biology of the CCL2/CCR2 axis as well as the role of this axis in COVID-19 immunopathogenesis, along with therapeutic options aimed at inhibiting CCL2/CCR2 and modulating dysregulated inflammatory responses in patients with severe SARS-CoV-2 infection.
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Affiliation(s)
- Mitra Ranjbar
- Department of Infectious Disease, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Rahimi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zeinab Baghernejadan
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Atousa Ghorbani
- Department of Biology, East Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Hossein Khorramdelazad
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
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15
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Li CZ, Chang HM, Hsu WL, Venkatesan P, Lin MHC, Lai PS. Curcumin-Loaded Oil-Free Self-Assembled Micelles Inhibit the Influenza A Virus Activity and the Solidification of Curcumin-Loaded Micelles for Pharmaceutical Applications. Pharmaceutics 2022; 14:2422. [PMID: 36365240 PMCID: PMC9697350 DOI: 10.3390/pharmaceutics14112422] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 10/28/2022] [Accepted: 11/02/2022] [Indexed: 08/30/2023] Open
Abstract
Curcumin, a well-known natural lipophilic phenolic compound, plays a vital role in inhibiting the influenza infection. Currently, many kinds of formulations for the enhancement of a water dispersion of curcumin have been developed; however, the anti-influenza abilities of formulated curcumin have been much less investigated. In this study, the optimized self-assembled micelles of RH 40/Tween 80 loaded with curcumin (Cur-M) in an oil-free-based system were spherical with a hydrodynamic size at 13.55 nm ± 0.208 and polydispersity at 0.144 characterized by atomic force microscopy and dynamic light scattering, respectively. Additionally, Cur-M significantly increased the bioactivity/stability of curcumin and effectively inhibited the influenza A virus infection and its replication after viral entry, indicating the alteration of the inhibition mechanisms of curcumin against virus infection via RH 40/Tween 80 micelle formulation. Furthermore, a solid formulation (Cur-SM) of Cur-M was successfully developed by a one-pot physical adsorption method using a small amount of adsorbent and ~50% of curcumin/Cur-M that could be burst released from Cur-SM in 1 h, facilitating the fast-releasing applications. Ultimately, all of the results show that Cur-SM acts as a good nano-formulation of curcumin with improved solubility/dispersity in aqueous solutions and demonstrate new anti-influenza mechanisms of curcumin for pharmaceutical development.
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Affiliation(s)
- Cun-Zhao Li
- Department of Chemistry, National Chung Hsing University, No. 145, Xingda Road, Taichung 402, Taiwan
| | - Hui-Min Chang
- Graduate Institute of Microbiology and Public Health, National Chung Hsing University, No. 145, Xingda Road, Taichung 402, Taiwan
| | - Wei-Li Hsu
- Graduate Institute of Microbiology and Public Health, National Chung Hsing University, No. 145, Xingda Road, Taichung 402, Taiwan
| | - Parthiban Venkatesan
- Department of Chemistry, National Chung Hsing University, No. 145, Xingda Road, Taichung 402, Taiwan
| | - Martin Hsiu-Chu Lin
- Department of Chemistry, National Chung Hsing University, No. 145, Xingda Road, Taichung 402, Taiwan
- Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, No. 145, Xingda Road, Taichung 402, Taiwan
- Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi Branch, Chia-Yi 613, Taiwan
| | - Ping-Shan Lai
- Department of Chemistry, National Chung Hsing University, No. 145, Xingda Road, Taichung 402, Taiwan
- Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, No. 145, Xingda Road, Taichung 402, Taiwan
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16
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Optimization of Anti-SARS-CoV-2 Treatments Based on Curcumin, Used Alone or Employed as a Photosensitizer. Viruses 2022; 14:v14102132. [PMID: 36298687 PMCID: PMC9608677 DOI: 10.3390/v14102132] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/23/2022] [Accepted: 09/25/2022] [Indexed: 11/16/2022] Open
Abstract
Curcumin, the bioactive compound of the spice Curcuma longa, has already been reported as a potential COVID-19 adjuvant treatment due to its immunomodulatory and anti-inflammatory properties. In this study, SARS-CoV-2 was challenged with curcumin; moreover, curcumin was also coupled with laser light at 445 nm in a photodynamic therapy approach. Curcumin at a concentration of 10 μM, delivered to the virus prior to inoculation on cell culture, inhibited SARS-CoV-2 replication (reduction >99%) in Vero E6 cells, possibly due to disruption of the virion structure, as observed using the RNase protection assay. However, curcumin was not effective as a prophylactic treatment on already-infected Vero E6 cells. Notably, when curcumin was employed as a photosensitizer and blue laser light at 445 nm was delivered to a mix of curcumin/virus prior to the inoculation on the cells, virus inactivation was observed (>99%) using doses of curcumin that were not antiviral by themselves. Photodynamic therapy employing crude curcumin can be suggested as an antiviral option against SARS-CoV-2 infection.
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17
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Antiviral perspectives of economically important Indian medicinal plants and spices. PROCEEDINGS OF THE INDIAN NATIONAL SCIENCE ACADEMY 2022. [PMCID: PMC9422945 DOI: 10.1007/s43538-022-00099-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Human respiratory diseases caused by viral infections leads to morbidity. Among infectious diseases, viral infections associated with the respiratory tract remain the primary reason for global deaths due to their transmissibility. Since immemorial, traditional Indian medicinal plants, their extracts, and several phytochemicals can treat various diseases. Sources for this review paper are data derived from a peer-reviewed journal that emphasizes the economic importance of medicinal plants. Several plant-based medicines have been reported to be effective against multiple viral infections, including the Human Adenovirus, Enterovirus, Influenza virus, Hepatitis virus, etc. This review emphasizes use of the Indian medicinal plants like as Withania somnifera (Ashwagandha, Winter Cherry), Moringa oleifera (Drumstick), Ocimum tenuiflorum (Tulsi), Azadirachta indica (Neem), Curcuma longa (Turmeric), Terminalia chebula (Chebulic Myrobalan), Punica granatum (Pomegranate) and the Indian household spices (ginger, garlic and black pepper). It further describes their secondary phytoconstituents extraction procedure, mode of action and the potential application to improve clinical outcomes of neutraceuticals against various viral infections.
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Sivani BM, Azzeh M, Patnaik R, Pantea Stoian A, Rizzo M, Banerjee Y. Reconnoitering the Therapeutic Role of Curcumin in Disease Prevention and Treatment: Lessons Learnt and Future Directions. Metabolites 2022; 12:metabo12070639. [PMID: 35888763 PMCID: PMC9320502 DOI: 10.3390/metabo12070639] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 06/30/2022] [Accepted: 07/08/2022] [Indexed: 02/04/2023] Open
Abstract
Turmeric is a plant with a very long history of medicinal use across different cultures. Curcumin is the active part of turmeric, which has exhibited various beneficial physiological and pharmacological effects. This review aims to critically appraise the corpus of literature associated with the above pharmacological properties of curcumin, with a specific focus on antioxidant, anti-inflammatory, anticancer and antimicrobial properties. We have also reviewed the different extraction strategies currently in practice, highlighting the strengths and drawbacks of each technique. Further, our review also summarizes the clinical trials that have been conducted with curcumin, which will allow the reader to get a quick insight into the disease/patient population of interest with the outcome that was investigated. Lastly, we have also highlighted the research areas that need to be further scrutinized to better grasp curcumin’s beneficial physiological and medicinal properties, which can then be translated to facilitate the design of better bioactive therapeutic leads.
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Affiliation(s)
- Bala Mohan Sivani
- Banerjee Research Group, College of Medicine and Health Sciences, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai 505055, United Arab Emirates; (B.M.S.); (M.A.); (R.P.)
| | - Mahmoud Azzeh
- Banerjee Research Group, College of Medicine and Health Sciences, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai 505055, United Arab Emirates; (B.M.S.); (M.A.); (R.P.)
| | - Rajashree Patnaik
- Banerjee Research Group, College of Medicine and Health Sciences, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai 505055, United Arab Emirates; (B.M.S.); (M.A.); (R.P.)
| | - Anca Pantea Stoian
- Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, 020022 Bucharest, Romania;
| | - Manfredi Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, 90128 Palermo, Italy;
| | - Yajnavalka Banerjee
- Banerjee Research Group, College of Medicine and Health Sciences, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai 505055, United Arab Emirates; (B.M.S.); (M.A.); (R.P.)
- Centre for Medical Education, University of Dundee, Dundee DD1 4HN, UK
- Correspondence: or ; Tel.: +971-527-873-636
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19
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Liu S, Liu J, He L, Liu L, Cheng B, Zhou F, Cao D, He Y. A Comprehensive Review on the Benefits and Problems of Curcumin with Respect to Human Health. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27144400. [PMID: 35889273 PMCID: PMC9319031 DOI: 10.3390/molecules27144400] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 07/01/2022] [Accepted: 07/05/2022] [Indexed: 12/03/2022]
Abstract
Curcumin is the most important active component in turmeric extracts. Curcumin, a natural monomer from plants has received a considerable attention as a dietary supplement, exhibiting evident activity in a wide range of human pathological conditions. In general, curcumin is beneficial to human health, demonstrating pharmacological activities of anti-inflammation and antioxidation, as well as antitumor and immune regulation activities. Curcumin also presents therapeutic potential in neurodegenerative, cardiovascular and cerebrovascular diseases. In this review article, we summarize the advancements made in recent years with respect to curcumin as a biologically active agent in malignant tumors, Alzheimer’s disease (AD), hematological diseases and viral infectious diseases. We also focus on problems associated with curcumin from basic research to clinical translation, such as its low solubility, leading to poor bioavailability, as well as the controversy surrounding the association between curcumin purity and effect. Through a review and summary of the clinical research on curcumin and case reports of adverse effects, we found that the clinical transformation of curcumin is not successful, and excessive intake of curcumin may have adverse effects on the kidneys, heart, liver, blood and immune system, which leads us to warn that curcumin has a long way to go from basic research to application transformation.
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Affiliation(s)
- Siyu Liu
- Post-Graduate School, Hunan University of Chinese Medicine, Changsha 410208, China; (S.L.); (J.L.); (L.L.); (F.Z.)
| | - Jie Liu
- Post-Graduate School, Hunan University of Chinese Medicine, Changsha 410208, China; (S.L.); (J.L.); (L.L.); (F.Z.)
| | - Lan He
- The First Clinical College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410007, China; (L.H.); (B.C.)
| | - Liu Liu
- Post-Graduate School, Hunan University of Chinese Medicine, Changsha 410208, China; (S.L.); (J.L.); (L.L.); (F.Z.)
| | - Bo Cheng
- The First Clinical College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410007, China; (L.H.); (B.C.)
| | - Fangliang Zhou
- Post-Graduate School, Hunan University of Chinese Medicine, Changsha 410208, China; (S.L.); (J.L.); (L.L.); (F.Z.)
- Hunan Provincial Engineering and Technological Research Center for Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Chinese Medicine and Protecting Visual Function, Hunan University of Chinese Medicine, Changsha 410208, China
| | - Deliang Cao
- Post-Graduate School, Hunan University of Chinese Medicine, Changsha 410208, China; (S.L.); (J.L.); (L.L.); (F.Z.)
- Correspondence: (D.C.); (Y.H.)
| | - Yingchun He
- Post-Graduate School, Hunan University of Chinese Medicine, Changsha 410208, China; (S.L.); (J.L.); (L.L.); (F.Z.)
- Hunan Provincial Engineering and Technological Research Center for Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Chinese Medicine and Protecting Visual Function, Hunan University of Chinese Medicine, Changsha 410208, China
- Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
- Correspondence: (D.C.); (Y.H.)
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20
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Wang X, Chen Y, Shi H, Zou P. Erythromycin Estolate Is a Potent Inhibitor Against HCoV-OC43 by Directly Inactivating the Virus Particle. Front Cell Infect Microbiol 2022; 12:905248. [PMID: 35873167 PMCID: PMC9301004 DOI: 10.3389/fcimb.2022.905248] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Accepted: 06/10/2022] [Indexed: 12/22/2022] Open
Abstract
In addition to antibacterial effects, macrolide antibiotics exhibit other extensive pharmacological effects, such as anti-inflammatory and antiviral activities. Erythromycin estolate, one of the macrolide antibiotics, was previously investigated to effectively inhibit infections of various flaviviruses including Zika virus, dengue virus, and yellow fever virus, but its antiviral effect against human coronavirus remains unknown. Thus, the current study was designed to evaluate the antiviral efficacy of erythromycin estolate against human coronavirus strain OC43 (HCoV-OC43) and to illustrate the underlying mechanisms. Erythromycin estolate effectively inhibited HCoV-OC43 infection in different cell types and significantly reduced virus titers at safe concentration without cell cytotoxicity. Furthermore, erythromycin estolate was identified to inhibit HCoV-OC43 infection at the early stage and to irreversibly inactivate virus by disrupting the integrity of the viral membrane whose lipid component might be the target of action. Together, it was demonstrated that erythromycin estolate could be a potential therapeutic drug for HCoV-OC43 infection.
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Affiliation(s)
- Xiaohuan Wang
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yongkang Chen
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
| | - Huichun Shi
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Peng Zou
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
- *Correspondence: Peng Zou,
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21
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Ferreira LLC, Abreu MP, Costa CB, Leda PO, Behrens MD, Dos Santos EP. Curcumin and Its Analogs as a Therapeutic Strategy in Infections Caused by RNA Genome Viruses. FOOD AND ENVIRONMENTAL VIROLOGY 2022; 14:120-137. [PMID: 35352306 PMCID: PMC8963406 DOI: 10.1007/s12560-022-09514-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 02/09/2022] [Indexed: 05/03/2023]
Abstract
The use of natural resources for the prevention and treatment of diseases considered fatal to humanity has evolved. Several medicinal plants have nutritional and pharmacological potential in the prevention and treatment of viral infections, among them, turmeric, which is recognized for its biological properties associated with curcuminoids, mainly represented by curcumin, and found mostly in rhizomes. The purpose of this review was to compile the pharmacological activities of curcumin and its analogs, aiming at stimulating their use as a therapeutic strategy to treat infections caused by RNA genome viruses. We revisited its historical application as an anti-inflammatory, antioxidant, and antiviral agent that combined with low toxicity, motivated research against viruses affecting the population for decades. Most findings concentrate particularly on arboviruses, HIV, and the recent SARS-CoV-2. As one of the main conclusions, associating curcuminoids with nanomaterials increases solubility, bioavailability, and antiviral effects, characterized by blocking the entry of the virus into the cell or by inhibiting key enzymes in viral replication and transcription.
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Affiliation(s)
- Leide Lene C Ferreira
- Herbal Medicines Department, Vital Brazil Institute, Maestro José Botelho, 64, Santa Rosa, CEP 24.230-340, Niterói, RJ, Brazil.
- Galenic Development Laboratory, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
| | - Marina P Abreu
- Herbal Medicines Department, Vital Brazil Institute, Maestro José Botelho, 64, Santa Rosa, CEP 24.230-340, Niterói, RJ, Brazil
| | - Camila B Costa
- Technological Development and Innovation Laboratory, Vital Brazil Institute, Rio de Janeiro, Brazil
| | - Paulo O Leda
- Laboratory of Natural Products for Public Health, Institute of Pharmaceutical Technology, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Maria Dutra Behrens
- Laboratory of Natural Products for Public Health, Institute of Pharmaceutical Technology, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Elisabete Pereira Dos Santos
- Galenic Development Laboratory, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
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22
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A Review on the Potential Species of the Zingiberaceae Family with Anti-viral Efficacy Towards Enveloped Viruses. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2022. [DOI: 10.22207/jpam.16.2.35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Natural products are a great wellspring of biodiversity for finding novel antivirals, exposing new interactions between structure and operation and creating successful defensive or remedial methodologies against viral diseases. The members of Zingiberaceae traditional plant and herbal products have robust anti-viral action, and their findings will further lead to the production of derivatives and therapeutic. Additionally, it highlights the insight of utilizing these phytoextracts or their constituent compounds as an emergency prophylactic medicine during the pandemic or endemic situations for novel viruses. In this connection, this review investigates the potential candidates of the Zingiberaceae family, consisting of bioactive phytocompounds with proven antiviral efficacy against enveloped viruses. The present study was based on published antiviral efficacy of Curcuma longa, Zingiber officinale, Kaempferia parviflora, Aframomum melegueta Elettaria cardamomum, Alpina Sps (belongs to the Zingiberaceae family) towards the enveloped viruses. The relevant data was searched in Scopus”, “Scifinder”, “Springer”, “Pubmed”, “Google scholar” “Wiley”, “Web of Science”, “Cochrane “Library”, “Embase”, Dissertations, theses, books, and technical reports. Meticulously articles were screened with the subject relevancy and categorized for their ethnopharmacological significance with in-depth analysis. We have comprehensively elucidated the antiviral potency of phytoextracts, major composition, key compounds, mode of action, molecular evidence, immunological relevance, and potential bioactive phytocompounds of these five species belonging to the Zingiberaceae family. Conveniently, these phytoextracts exhibited multimode activity in combating the dreadful enveloped viruses.
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23
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Omer AK, Khorshidi S, Mortazavi N, Rahman HS. A Review on the Antiviral Activity of Functional Foods Against COVID-19 and Viral Respiratory Tract Infections. Int J Gen Med 2022; 15:4817-4835. [PMID: 35592539 PMCID: PMC9112189 DOI: 10.2147/ijgm.s361001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 04/12/2022] [Indexed: 11/23/2022] Open
Abstract
Due to the absence of successful therapy, vaccines for protection are continuously being developed. Since vaccines must be thoroughly tested, viral respiratory tract infections (VRTIs), mainly coronaviruses, have seriously affected human health worldwide in recent years. In this review, we presented the relevant data which originated from trusted publishers regarding the practical benefits of functional foods (FFs) and their dietary sources, in addition to natural plant products, in viral respiratory and COVID-19 prevention and immune-boosting activities. As a result, FFs were confirmed to be functionally active ingredients for preventing COVID-19 and VRTIs. Furthermore, the antiviral activity and immunological effects of FFs against VRTIs and COVID-19 and their potential main mechanisms of action are also being reviewed. Therefore, to prevent COVID-19 and VRTIs, it is critical to identify controlling the activities and immune-enhancing functional food constituents as early as possible. We further aimed to summarize functional food constituents as a dietary supplement that aids in immune system boosting and may effectively reduce VRTIs and COVID-19 and promote therapeutic efficacy.
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Affiliation(s)
- Abdullah Khalid Omer
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
- Razga Company, Sulaimaniyah, Kurdistan Region, Iraq
| | - Sonia Khorshidi
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
| | - Negar Mortazavi
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
| | - Heshu Sulaiman Rahman
- Department of Physiology, College of Medicine, University of Sulaimani, Sulaimaniyah, Iraq
- Department of Medical Laboratory Sciences, Komar University of Science and Technology, Sulaimaniyah, Iraq
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Oluwole DO, Coleman L, Buchanan W, Chen T, La Ragione RM, Liu LX. Antibiotics-Free Compounds for Chronic Wound Healing. Pharmaceutics 2022; 14:pharmaceutics14051021. [PMID: 35631606 PMCID: PMC9143489 DOI: 10.3390/pharmaceutics14051021] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 04/04/2022] [Accepted: 05/05/2022] [Indexed: 02/05/2023] Open
Abstract
The rapid rise in the health burden associated with chronic wounds is of great concern to policymakers, academia, and industry. This could be attributed to the devastating implications of this condition, and specifically, chronic wounds which have been linked to invasive microbial infections affecting patients' quality of life. Unfortunately, antibiotics are not always helpful due to their poor penetration of bacterial biofilms and the emergence of antimicrobial resistance. Hence, there is an urgent need to explore antibiotics-free compounds/formulations with proven or potential antimicrobial, anti-inflammatory, antioxidant, and wound healing efficacy. The mechanism of antibiotics-free compounds is thought to include the disruption of the bacteria cell structure, preventing cell division, membrane porins, motility, and the formation of a biofilm. Furthermore, some of these compounds foster tissue regeneration by modulating growth factor expression. In this review article, the focus is placed on a number of non-antibiotic compounds possessing some of the aforementioned pharmacological and physiological activities. Specific interest is given to Aloevera, curcumin, cinnamaldehyde, polyhexanide, retinoids, ascorbate, tocochromanols, and chitosan. These compounds (when alone or in formulation with other biologically active molecules) could be a dependable alternative in the management or prevention of chronic wounds.
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Affiliation(s)
- David O. Oluwole
- Chemical and Process Engineering Department, Faculty of Engineering and Physical Science, University of Surrey, Guildford GU2 7XH, UK; (L.C.); (T.C.)
- Correspondence: (D.O.O.); (L.X.L.)
| | - Lucy Coleman
- Chemical and Process Engineering Department, Faculty of Engineering and Physical Science, University of Surrey, Guildford GU2 7XH, UK; (L.C.); (T.C.)
| | | | - Tao Chen
- Chemical and Process Engineering Department, Faculty of Engineering and Physical Science, University of Surrey, Guildford GU2 7XH, UK; (L.C.); (T.C.)
| | - Roberto M. La Ragione
- School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK;
- School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7AL, UK
| | - Lian X. Liu
- Chemical and Process Engineering Department, Faculty of Engineering and Physical Science, University of Surrey, Guildford GU2 7XH, UK; (L.C.); (T.C.)
- Correspondence: (D.O.O.); (L.X.L.)
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Chen Y, Wang X, Shi H, Zou P. Montelukast Inhibits HCoV-OC43 Infection as a Viral Inactivator. Viruses 2022; 14:v14050861. [PMID: 35632604 PMCID: PMC9143845 DOI: 10.3390/v14050861] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 04/11/2022] [Accepted: 04/13/2022] [Indexed: 02/06/2023] Open
Abstract
Coronaviruses (CoVs) consist of a large group of RNA viruses causing various diseases in humans and in lots of animals. Human coronavirus (HCoV) OC43, the prototype of beta-coronavirus discovered in the 1960s, has been circulating in humans for long time, and infection with other emerging strains of beta-coronavirus (SARS-CoV, SARS-CoV-2, and MERS-CoV) can lead to severe illness and death. In this study, we found that montelukast, a leukotriene receptor antagonist, potently inhibited the infection of HCoV-OC43 in distinct cells in a dose- and time- dependent manner. Additionally, the results showed that montelukast induced release of HCoV-OC43 genomic RNA by disrupting the integrity of the viral lipid membrane, and irreversibly inhibited viral infection. Considering the similarity among HCoV-OC43, MERS-CoV, and SARS-CoV-2, it suggests that montelukast may be a potential candidate for the treatment of human beta-coronavirus infection.
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Affiliation(s)
| | | | | | - Peng Zou
- Correspondence: ; Tel.: +86-21-3799-0333 (ext. 5273)
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Wang Y, Dan K, Xue X, Chen B, Chen C. Curcumin assists anti-EV71 activity of IFN-α by inhibiting IFNAR1 reduction in SH-SY5Y cells. Gut Pathog 2022; 14:8. [PMID: 35151347 PMCID: PMC8840321 DOI: 10.1186/s13099-022-00481-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 02/01/2022] [Indexed: 12/30/2022] Open
Abstract
Background and aim Enterovirus 71(EV71) can cause severe hand, foot, and mouth disease (HFMD) with brain tissue involvement. Few effective anti-EV71 drugs are presently available in clinical practice. Interferon-α (IFN-α) was ineffective while Curcumin was effective in restricting EV71 replication in non-neuronal cells. Ubiquitin–proteasome-mediated degradation of interferon-alpha receptor 1 (IFNAR1) protein contributes to IFN-α resistance. Current study aimed to determine synergistic inhibition of EV71 by Curcumin and IFN-α in human neuroblastoma SH-SY5Y cells. Methods SH-SY5Y cells were infected with mock-/Curcumin-pre-incubated EV71 or transfected with plasmid containing interferon-stimulated response element (ISRE) or mRNA containing viral internal ribosomal entry site (IRES) following by post-treatment with Curcumin with or without IFN-α. Supernatant IFN-α/β was detected by ELISA. ISRE, IRSE, proteasome and deubiquitinating activity were measured by luciferase assay. EV71 RNA and viral protein or IFNAR1 were determined by qPCR and western blot, respectively. Results EV71 flailed to completely block IFN-α/β production but inhibited IFN-α signal. Curcumin only slightly inhibited EV71 proliferation without modulating virus attachment and internalization. However, Curcumin addition restored IFN-α-mediated ISRE activity thus significantly inhibiting EV71 replication. Furthermore, EV71 also reduced IFNAR1 protein with proteasome-dependence in SH-SY5Y cells, which can be reversed by Curcumin addition with the evidence that it lowered proteasome activity. Conclusion These data demonstrate that Curcumin assists anti-EV71 activity of IFN-α by inhibiting IFNAR1 reduction via ubiquitin–proteasome disruption in SH-SY5Y cells.
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Islam MT, Quispe C, Martorell M, Docea AO, Salehi B, Calina D, Reiner Ž, Sharifi-Rad J. Dietary supplements, vitamins and minerals as potential interventions against viruses: Perspectives for COVID-19. INT J VITAM NUTR RES 2022; 92:49-66. [PMID: 33435749 DOI: 10.1024/0300-9831/a000694] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
The novel coronavirus (SARS-CoV-2) causing COVID-19 disease pandemic has infected millions of people and caused more than thousands of deaths in many countries across the world. The number of infected cases is increasing day by day. Unfortunately, we do not have a vaccine and specific treatment for it. Along with the protective measures, respiratory and/or circulatory supports and some antiviral and retroviral drugs have been used against SARS-CoV-2, but there are no more extensive studies proving their efficacy. In this study, the latest publications in the field have been reviewed, focusing on the modulatory effects on the immunity of some natural antiviral dietary supplements, vitamins and minerals. Findings suggest that several dietary supplements, including black seeds, garlic, ginger, cranberry, orange, omega-3 and -6 polyunsaturated fatty acids, vitamins (e.g., A, B vitamins, C, D, E), and minerals (e.g., Cu, Fe, Mg, Mn, Na, Se, Zn) have anti-viral effects. Many of them act against various species of respiratory viruses, including severe acute respiratory syndrome-related coronaviruses. Therefore, dietary supplements, including vitamins and minerals, probiotics as well as individual nutritional behaviour can be used as adjuvant therapy together with antiviral medicines in the management of COVID-19 disease.
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Affiliation(s)
- Muhammad Torequl Islam
- Department of Pharmacy, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Bangladesh
| | - Cristina Quispe
- Facultad de Ciencias de la Salud, Universidad Arturo Prat, Chile
| | - Miquel Martorell
- Department of Nutrition and Dietetics, Faculty of Pharmacy, and Centre for Healthy Living, University of Concepción, Concepción, Chile
- Universidad de Concepción, Unidad de Desarrollo Tecnológico (UDT), Concepción, Chile
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, Romania
| | - Bahare Salehi
- Medical Ethics and Law Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, Romania
| | - Željko Reiner
- Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Croatia
| | - Javad Sharifi-Rad
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador
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Yang J, Liu S. Influenza Virus Entry inhibitors. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1366:123-135. [DOI: 10.1007/978-981-16-8702-0_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Antiviral Therapeutic Potential of Curcumin: An Update. Molecules 2021; 26:molecules26226994. [PMID: 34834089 PMCID: PMC8617637 DOI: 10.3390/molecules26226994] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/15/2021] [Accepted: 11/16/2021] [Indexed: 01/10/2023] Open
Abstract
The treatment of viral disease has become a medical challenge because of the increasing incidence and prevalence of human viral pathogens, as well as the lack of viable treatment alternatives, including plant-derived strategies. This review attempts to investigate the trends of research on in vitro antiviral effects of curcumin against different classes of human viral pathogens worldwide. Various electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar were searched for published English articles evaluating the anti-viral activity of curcumin. Data were then extracted and analyzed. The forty-three studies (published from 1993 to 2020) that were identified contain data for 24 different viruses. The 50% cytotoxic concentration (CC50), 50% effective/inhibitory concentration (EC50/IC50), and stimulation index (SI) parameters showed that curcumin had antiviral activity against viruses causing diseases in humans. Data presented in this review highlight the potential antiviral applications of curcumin and open new avenues for further experiments on the clinical applications of curcumin and its derivatives.
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Kim M, Cho H, Ahn DG, Jung HG, Seo HY, Kim JS, Lee YJ, Choi JY, Park IH, Shin JS, Kim SJ, Oh JW. In Vitro Replication Inhibitory Activity of Xanthorrhizol against Severe Acute Respiratory Syndrome Coronavirus 2. Biomedicines 2021; 9:1725. [PMID: 34829954 PMCID: PMC8615586 DOI: 10.3390/biomedicines9111725] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 11/16/2021] [Accepted: 11/16/2021] [Indexed: 12/24/2022] Open
Abstract
In spite of the large number of repositioned drugs and direct-acting antivirals in clinical trials for the management of the ongoing COVID-19 pandemic, there are few cost-effective therapeutic options for severe acute respiratory syndrome (SARS) coronavirus 2 (SCoV2) infection. In this paper, we show that xanthorrhizol (XNT), a bisabolane-type sesquiterpenoid compound isolated from the Curcuma xanthorrhizza Roxb., a ginger-line plant of the family Zingiberaceae, displays a potent antiviral efficacy in vitro against SCoV2 and other related coronaviruses, including SARS-CoV-1 (SCoV1) and a common cold-causing human coronavirus. XNT reduced infectious SCoV2 titer by ~3-log10 at 20 μM and interfered with the replication of the SCoV1 subgenomic replicon, while it had no significant antiviral effects against hepatitis C virus and noroviruses. Further, XNT exerted similar antiviral functions against SCoV2 variants, such as a GH clade strain and a delta strain currently predominant worldwide. Neither SCoV2 entry into cells nor the enzymatic activity of viral RNA polymerase (Nsp12), RNA helicase (Nsp13), or the 3CL main protease (Nsp5) was inhibited by XNT. While its CoV replication inhibitory mechanism remains elusive, our results demonstrate that the traditional folk medicine XNT could be a promising antiviral candidate that inhibits a broad range of SCoV2 variants of concern and other related CoVs.
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Affiliation(s)
- Minwoo Kim
- Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; (M.K.); (H.C.); (D.-G.A.); (H.-G.J.); (H.Y.S.); (J.-S.K.)
| | - Hee Cho
- Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; (M.K.); (H.C.); (D.-G.A.); (H.-G.J.); (H.Y.S.); (J.-S.K.)
| | - Dae-Gyun Ahn
- Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; (M.K.); (H.C.); (D.-G.A.); (H.-G.J.); (H.Y.S.); (J.-S.K.)
| | - Hae-Gwang Jung
- Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; (M.K.); (H.C.); (D.-G.A.); (H.-G.J.); (H.Y.S.); (J.-S.K.)
| | - Han Young Seo
- Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; (M.K.); (H.C.); (D.-G.A.); (H.-G.J.); (H.Y.S.); (J.-S.K.)
| | - Ji-Su Kim
- Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; (M.K.); (H.C.); (D.-G.A.); (H.-G.J.); (H.Y.S.); (J.-S.K.)
| | - Youn-Jung Lee
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (Y.-J.L.); (J.Y.C.)
| | - Jun Yong Choi
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (Y.-J.L.); (J.Y.C.)
| | - In Ho Park
- Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Korea; (I.H.P.); (J.-S.S.)
| | - Jeon-Soo Shin
- Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Korea; (I.H.P.); (J.-S.S.)
- Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Seong-Jun Kim
- Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea;
| | - Jong-Won Oh
- Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; (M.K.); (H.C.); (D.-G.A.); (H.-G.J.); (H.Y.S.); (J.-S.K.)
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Marín-Palma D, Tabares-Guevara JH, Zapata-Cardona MI, Flórez-Álvarez L, Yepes LM, Rugeles MT, Zapata-Builes W, Hernandez JC, Taborda NA. Curcumin Inhibits In Vitro SARS-CoV-2 Infection In Vero E6 Cells through Multiple Antiviral Mechanisms. Molecules 2021; 26:6900. [PMID: 34833991 PMCID: PMC8618354 DOI: 10.3390/molecules26226900] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 11/05/2021] [Accepted: 11/11/2021] [Indexed: 01/14/2023] Open
Abstract
Due to the scarcity of therapeutic approaches for COVID-19, we investigated the antiviral and anti-inflammatory properties of curcumin against SARS-CoV-2 using in vitro models. The cytotoxicity of curcumin was evaluated using MTT assay in Vero E6 cells. The antiviral activity of this compound against SARS-CoV-2 was evaluated using four treatment strategies (i. pre-post infection treatment, ii. co-treatment, iii. pre-infection, and iv. post-infection). The D614G strain and Delta variant of SARS-CoV-2 were used, and the viral titer was quantified by plaque assay. The anti-inflammatory effect was evaluated in peripheral blood mononuclear cells (PBMCs) using qPCR and ELISA. By pre-post infection treatment, Curcumin (10 µg/mL) exhibited antiviral effect of 99% and 99.8% against DG614 strain and Delta variant, respectively. Curcumin also inhibited D614G strain by pre-infection and post-infection treatment. In addition, curcumin showed a virucidal effect against D614G strain and Delta variant. Finally, the pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) released by PBMCs triggered by SARS-CoV-2 were decreased after treatment with curcumin. Our results suggest that curcumin affects the SARS-CoV-2 replicative cycle and exhibits virucidal effect with a variant/strain independent antiviral effect and immune-modulatory properties. This is the first study that showed a combined (antiviral/anti-inflammatory) effect of curcumin during SARS-CoV-2 infection. However, additional studies are required to define its use as a treatment for the COVID-19.
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Affiliation(s)
- Damariz Marín-Palma
- Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, 050012 Medellín, Colombia; (D.M.-P.); (J.H.T.-G.); (W.Z.-B.); (J.C.H.)
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, UdeA, 050010 Medellín, Colombia; (M.I.Z.-C.); (L.F.-Á.); (L.M.Y.); (M.T.R.)
| | - Jorge H. Tabares-Guevara
- Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, 050012 Medellín, Colombia; (D.M.-P.); (J.H.T.-G.); (W.Z.-B.); (J.C.H.)
| | - María I. Zapata-Cardona
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, UdeA, 050010 Medellín, Colombia; (M.I.Z.-C.); (L.F.-Á.); (L.M.Y.); (M.T.R.)
| | - Lizdany Flórez-Álvarez
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, UdeA, 050010 Medellín, Colombia; (M.I.Z.-C.); (L.F.-Á.); (L.M.Y.); (M.T.R.)
| | - Lina M. Yepes
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, UdeA, 050010 Medellín, Colombia; (M.I.Z.-C.); (L.F.-Á.); (L.M.Y.); (M.T.R.)
| | - Maria T. Rugeles
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, UdeA, 050010 Medellín, Colombia; (M.I.Z.-C.); (L.F.-Á.); (L.M.Y.); (M.T.R.)
| | - Wildeman Zapata-Builes
- Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, 050012 Medellín, Colombia; (D.M.-P.); (J.H.T.-G.); (W.Z.-B.); (J.C.H.)
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, UdeA, 050010 Medellín, Colombia; (M.I.Z.-C.); (L.F.-Á.); (L.M.Y.); (M.T.R.)
| | - Juan C. Hernandez
- Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, 050012 Medellín, Colombia; (D.M.-P.); (J.H.T.-G.); (W.Z.-B.); (J.C.H.)
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, UdeA, 050010 Medellín, Colombia; (M.I.Z.-C.); (L.F.-Á.); (L.M.Y.); (M.T.R.)
| | - Natalia A. Taborda
- Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, 050012 Medellín, Colombia; (D.M.-P.); (J.H.T.-G.); (W.Z.-B.); (J.C.H.)
- Grupo de Investigaciones Biomédicas Uniremington, Programa de Medicina, Facultad de Ciencias de la Salud, Corporación Universitaria Remington, 050016 Medellín, Colombia
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Dound YA, Sehgal R. Preclinical Efficacy and Safety Studies of Formulation SSV-003, a Potent Anti-Viral Herbal Formulation. J Exp Pharmacol 2021; 13:913-921. [PMID: 34712064 PMCID: PMC8548056 DOI: 10.2147/jep.s310452] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 08/21/2021] [Indexed: 01/03/2023] Open
Abstract
Background Recent viral pandemics have challenged the global scientific community to immediately develop new therapies. The fastest approach to develop these is to explore natural products for their efficacies and repurposing of already approved molecules. Keeping global emergency in view, researchers at Shreepad Shree Vallabh SSV Phytopharmaceuticals developed the CurvicTM (SSV-003) formulation, comprising of curcumin, vitamin C, vitamin K2-7, selenomethionine and Zinc. Methods Researchers have systematically studied the SSV-003 formulation for its in vitro efficacy against influenza A virus (H1N1) (ATCC® VR-219™) and human beta coronavirus (ATCC® VR1558™) using MDCK & HCT-8 cell lines, respectively, in vivo efficacy studies of SSV-003 on influenza A virus infected Balb/c mice, and acute toxicity studies as per OECD guidelines. Results Formulation SSV-003 showed potent antiviral activities against both the selected virus strains. Its IC50 was significantly lessthan ribavirin against influenza A-H1N1-VR219, with no cytopathic effect. SSV-003 showed IC50 of 2.26 µg/mL against human beta coronavirus, which was near to the IC50 of ribavirin (2.25 µg/mL) and was less than remedisivir (6.23 µg/mL) with no cytopathic effect. In-vivo studies in an influenza A virus infected mice model showed a significantly higher TCID50 value in the infected control group as compared to test groups. Animals treated with SSV-003 showed a dose dependent decrease in TCID50. Formulation SSV-003 at the dose of 500, 1,000, and 1,500 mg/kg body weight showed 85.9%, 94.6%, and 95.1% decreases in infection as compared to the infected control group. Dose-dependent significant increases in CD4+, CD8+ counts, IgG and IgM levels were observed in SSV-003 treated groups as compared to the infected control group and remedisivir treated group. In the acute oral toxicity study, no mortality or morbidity was observed. Conclusion The data from these preclinical studies provide strong evidence of potent and safe antiviral and immunomodulatory activity of SSV-003.
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Affiliation(s)
- Yogesh Arun Dound
- Research and Development, Shreepad Shree Vallabh SSV Phytopharmaceuticals, Mumbai, Maharashtra, India
| | - Rajesh Sehgal
- Research and Development, Pharma Instinct Pvt. Ltd, Noida, Uttar Pradesh, India
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Caliskan UK, Karakus MM. Evaluation of botanicals as potential COVID-19 symptoms terminator. World J Gastroenterol 2021; 27:6551-6571. [PMID: 34754152 PMCID: PMC8554406 DOI: 10.3748/wjg.v27.i39.6551] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/01/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Information about the coronavirus disease 2019 (COVID-19) pandemic is still evolving since its appearance in December 2019 and has affected the whole world. Particularly, a search for an effective and safe treatment for COVID-19 continues. Botanical mixtures contain secondary metabolites (such as flavonoids, phenolics, alkaloids, essential oils etc.) with many therapeutic effects. In this study, the use of herbal treatments against COVID-19 was evaluated. Medical synthetic drugs focus mainly on respiratory symptoms, however herbal therapy with plant extracts may be useful to relieve overall symptoms of COVID-19 due to the variety of bioactive ingredients. Since COVID-19 is a virus that affects the respiratory tract, the antiviral effects of botanicals/plants against respiratory viruses have been examined through clinical studies. Data about COVID-19 patients revealed that the virus not only affects the respiratory system but different organs including the gastrointestinal (GI) system. As GI symptoms seriously affect quality of life, herbal options that might eliminate these problems were also evaluated. Finally, computer modeling studies of plants and their active compounds on COVID-19 were included. In summary, herbal therapies were identified as potential options for both antiviral effects and control of COVID-19 symptoms. Further data will be needed to enlighten all aspects of COVID-19 pathogenesis, before determining the effects of plants on severe acute respiratory syndrome coronavirus 2.
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Affiliation(s)
- Ufuk Koca Caliskan
- Department of Pharmacognosy and Pharmaceutical Botany, Gazi University, Ankara 06500, Turkey
| | - Methiye Mancak Karakus
- Department of Pharmacognosy and Pharmaceutical Botany, Gazi University, Ankara 06500, Turkey
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Nanaware N, Banerjee A, Mullick Bagchi S, Bagchi P, Mukherjee A. Dengue Virus Infection: A Tale of Viral Exploitations and Host Responses. Viruses 2021; 13:v13101967. [PMID: 34696397 PMCID: PMC8541669 DOI: 10.3390/v13101967] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 09/17/2021] [Accepted: 09/27/2021] [Indexed: 12/20/2022] Open
Abstract
Dengue is a mosquito-borne viral disease (arboviral) caused by the Dengue virus. It is one of the prominent public health problems in tropical and subtropical regions with no effective vaccines. Every year around 400 million people get infected by the Dengue virus, with a mortality rate of about 20% among the patients with severe dengue. The Dengue virus belongs to the Flaviviridae family, and it is an enveloped virus with positive-sense single-stranded RNA as the genetic material. Studies of the infection cycle of this virus revealed potential host targets important for the virus replication cycle. Here in this review article, we will be discussing different stages of the Dengue virus infection cycle inside mammalian host cells and how host proteins are exploited by the virus in the course of infection as well as how the host counteracts the virus by eliciting different antiviral responses.
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Affiliation(s)
- Nikita Nanaware
- Division of Virology, ICMR-National AIDS Research Institute, Pune 411026, MH, India; (N.N.); (A.B.)
| | - Anwesha Banerjee
- Division of Virology, ICMR-National AIDS Research Institute, Pune 411026, MH, India; (N.N.); (A.B.)
| | | | - Parikshit Bagchi
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Correspondence: or (P.B.); or (A.M.)
| | - Anupam Mukherjee
- Division of Virology, ICMR-National AIDS Research Institute, Pune 411026, MH, India; (N.N.); (A.B.)
- Correspondence: or (P.B.); or (A.M.)
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Thongsri P, Pewkliang Y, Borwornpinyo S, Wongkajornsilp A, Hongeng S, Sa-Ngiamsuntorn K. Curcumin inhibited hepatitis B viral entry through NTCP binding. Sci Rep 2021; 11:19125. [PMID: 34580340 PMCID: PMC8476618 DOI: 10.1038/s41598-021-98243-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 09/06/2021] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B virus (HBV) has been implicated in hepatitis and hepatocellular carcinoma. Current agents (nucleos(t)ide analogs and interferons) could only attenuate HBV infection. A combination of agents targeting different stages of viral life cycle (e.g., entry, replication, and cccDNA stability) was expected to eradicate the infection. Curcumin (CCM) was investigated for inhibitory action toward HBV attachment and internalization. Immortalized hepatocyte-like cells (imHCs), HepaRG and non-hepatic cells served as host cells for binding study with CCM. CCM decreased viral load, HBeAg, HBcAg (infectivity), intracellular HBV DNA, and cccDNA levels. The CCM-induced suppression of HBV entry was directly correlated with the density of sodium-taurocholate co-transporting polypeptide (NTCP), a known host receptor for HBV entry. The site of action of CCM was confirmed using TCA uptake assay. The affinity between CCM and NTCP was measured using isothermal titration calorimetry (ITC). These results demonstrated that CCM interrupted HBV entry and would therefore suppress HBV re-infection.
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Affiliation(s)
- Piyanoot Thongsri
- Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand.,Section for Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand
| | - Yongyut Pewkliang
- Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand.,Section for Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand
| | - Suparerk Borwornpinyo
- Excellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.,Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand
| | - Adisak Wongkajornsilp
- Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
| | - Suradej Hongeng
- Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.
| | - Khanit Sa-Ngiamsuntorn
- Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand.
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Curcumin Inhibits Replication of Human Parainfluenza Virus Type 3 by Affecting Viral Inclusion Body Formation. BIOMED RESEARCH INTERNATIONAL 2021; 2021:1807293. [PMID: 34409100 PMCID: PMC8367592 DOI: 10.1155/2021/1807293] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 07/19/2021] [Accepted: 07/28/2021] [Indexed: 12/30/2022]
Abstract
Human Parainfluenza Virus Type 3 (HPIV3) is one of the main pathogens that cause acute lower respiratory tract infections in infants and young children. However, there are currently no effective antiviral drugs and vaccines. Herein, we found that a natural compound, curcumin, inhibits HPIV3 infection and has antiviral effects on entry and replication of the virus life cycle. Immunofluorescence and western blotting experiments revealed that curcumin disrupts F-actin and inhibits viral inclusion body (IB) formation, thus inhibiting virus replication. Curcumin can also downregulate cellular PI4KB and interrupt its colocalization in viral IBs. This study verified the antiviral ability of curcumin on HPIV3 infection and preliminarily elucidated its influence on viral replication, providing a theoretical basis for antiviral drug development of HPIV3 and other parainfluenza viruses.
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Liu L, Deng CJ, Duan YL, Ye CJ, Gong DH, Guo XL, Lee WH, Zhou J, Li SA, Zhang Y. An Aerolysin-like Pore-Forming Protein Complex Targets Viral Envelope to Inactivate Herpes Simplex Virus Type 1. THE JOURNAL OF IMMUNOLOGY 2021; 207:888-901. [PMID: 34290105 DOI: 10.4049/jimmunol.2001056] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 05/20/2021] [Indexed: 01/12/2023]
Abstract
Because most of animal viruses are enveloped, cytoplasmic entry of these viruses via fusion with cellular membrane initiates their invasion. However, the strategies in which host cells counteract cytoplasmic entry of such viruses are incompletely understood. Pore-forming toxin aerolysin-like proteins (ALPs) exist throughout the animal kingdom, but their functions are mostly unknown. In this study, we report that βγ-crystallin fused aerolysin-like protein and trefoil factor complex (βγ-CAT), an ALP and trefoil factor complex from the frog Bombina maxima, directly blocks enveloped virus invasion by interfering with cytoplasmic entry. βγ-CAT targeted acidic glycosphingolipids on the HSV type 1 (HSV-1) envelope to induce pore formation, as indicated by the oligomer formation of protein and potassium and calcium ion efflux. Meanwhile, βγ-CAT formed ring-like oligomers of ∼10 nm in diameter on the liposomes and induced dye release from liposomes that mimic viral envelope. Unexpectedly, transmission electron microscopy analysis showed that the βγ-CAT-treated HSV-1 was visibly as intact as the vehicle-treated HSV-1, indicating that βγ-CAT did not lyse the viral envelope. However, the cytoplasmic entry of the βγ-CAT-treated HSV-1 into HeLa cells was totally hindered. In vivo, topical application of βγ-CAT attenuated the HSV-1 corneal infection in mice. Collectively, these results uncovered that βγ-CAT possesses the capacity to counteract enveloped virus invasion with its featured antiviral-acting manner. Our findings will also largely help to illustrate the putative antiviral activity of animal ALPs.
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Affiliation(s)
- Long Liu
- Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Science/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.,Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China
| | - Cheng-Jie Deng
- Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Science/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.,Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China
| | - Ya-Li Duan
- Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Science/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.,Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China
| | - Chen-Jun Ye
- Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Science/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China
| | - Dao-Hua Gong
- Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China.,Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Science/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China
| | - Xiao-Long Guo
- Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Science/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China
| | - Wen-Hui Lee
- Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Science/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China
| | - Jumin Zhou
- Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Science/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China;
| | - Sheng-An Li
- Department of Pathogen Biology and Immunology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China; and
| | - Yun Zhang
- Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Science/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; .,Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan, China
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38
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Witika BA, Makoni PA, Matafwali SK, Mweetwa LL, Shandele GC, Walker RB. Enhancement of Biological and Pharmacological Properties of an Encapsulated Polyphenol: Curcumin. Molecules 2021; 26:4244. [PMID: 34299519 PMCID: PMC8303961 DOI: 10.3390/molecules26144244] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 06/14/2021] [Accepted: 06/15/2021] [Indexed: 02/06/2023] Open
Abstract
There is a dearth of natural remedies available for the treatment of an increasing number of diseases facing mankind. Natural products may provide an opportunity to produce formulations and therapeutic solutions to address this shortage. Curcumin (CUR), diferuloylmethane; I,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione is the major pigment in turmeric powder which has been reported to exhibit a number of health benefits including, antibacterial, antiviral, anti-cancer, anti-inflammatory and anti-oxidant properties. In this review, the authors attempt to highlight the biological and pharmacological properties of CUR in addition to emphasizing aspects relating to the biosynthesis, encapsulation and therapeutic effects of the compound. The information contained in this review was generated by considering published information in which evidence of enhanced biological and pharmacological properties of nano-encapsulated CUR was reported. CUR has contributed to a significant improvement in melanoma, breast, lung, gastro-intestinal, and genito-urinary cancer therapy. We highlight the impact of nano-encapsulated CUR for efficient inhibition of cell proliferation, even at low concentrations compared to the free CUR when considering anti-proliferation. Furthermore nano-encapsulated CUR exhibited bioactive properties, exerted cytotoxic and anti-oxidant effects by acting on endogenous and cholinergic anti-oxidant systems. CUR was reported to block Hepatitis C virus (HCV) entry into hepatic cells, inhibit MRSA proliferation, enhance wound healing and reduce bacterial load. Nano-encapsulated CUR has also shown bioactive properties when acting on antioxidant systems (endogenous and cholinergic). Future research is necessary and must focus on investigation of encapsulated CUR nano-particles in different models of human pathology.
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Affiliation(s)
- Bwalya Angel Witika
- ApotheCom|A MEDiSTRAVA Company (Medical Division of Huntsworth), London WC2A 1AN, UK;
- Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Makhanda 6140, South Africa
| | - Pedzisai Anotida Makoni
- Division of Pharmacology, Faculty of Pharmacy, Rhodes University, Makhanda 6140, South Africa;
| | - Scott Kaba Matafwali
- Clinical Research Department, Faculty of Infectious and Tropical Diseases, LSHTM, London WC1E 7HT, UK;
| | - Larry Lawrence Mweetwa
- Department of Chemistry, Marine Biodiscovery Centre, University of Aberdeen, Aberdeen AB24 3FX, UK;
| | - Ginnethon Chaamba Shandele
- Department of Biochemistry, Institute of Basic and Biomedical Sciences, Levy Mwanawasa Medical University, P.O. Box 33991, Lusaka 10101, Zambia;
| | - Roderick Bryan Walker
- Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Makhanda 6140, South Africa
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39
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Shirey KA, Blanco JCG, Vogel SN. Targeting TLR4 Signaling to Blunt Viral-Mediated Acute Lung Injury. Front Immunol 2021; 12:705080. [PMID: 34282358 PMCID: PMC8285366 DOI: 10.3389/fimmu.2021.705080] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 06/10/2021] [Indexed: 01/14/2023] Open
Abstract
Respiratory viral infections have been a long-standing global burden ranging from seasonal recurrences to the unexpected pandemics. The yearly hospitalizations from seasonal viruses such as influenza can fluctuate greatly depending on the circulating strain(s) and the congruency with the predicted strains used for the yearly vaccine formulation, which often are not predicted accurately. While antiviral agents are available against influenza, efficacy is limited due to a temporal disconnect between the time of infection and symptom development and viral resistance. Uncontrolled, influenza infections can lead to a severe inflammatory response initiated by pathogen-associated molecular patterns (PAMPs) or host-derived danger-associated molecular patterns (DAMPs) that ultimately signal through pattern recognition receptors (PRRs). Overall, these pathogen-host interactions result in a local cytokine storm leading to acute lung injury (ALI) or the more severe acute respiratory distress syndrome (ARDS) with concomitant systemic involvement and more severe, life threatening consequences. In addition to traditional antiviral treatments, blocking the host's innate immune response may provide a more viable approach to combat these infectious pathogens. The SARS-CoV-2 pandemic illustrates a critical need for novel treatments to counteract the ALI and ARDS that has caused the deaths of millions worldwide. This review will examine how antagonizing TLR4 signaling has been effective experimentally in ameliorating ALI and lethal infection in challenge models triggered not only by influenza, but also by other ALI-inducing viruses.
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Affiliation(s)
- Kari Ann Shirey
- Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD, United States
| | | | - Stefanie N. Vogel
- Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD, United States
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40
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Goc A, Sumera W, Rath M, Niedzwiecki A. Phenolic compounds disrupt spike-mediated receptor-binding and entry of SARS-CoV-2 pseudo-virions. PLoS One 2021; 16:e0253489. [PMID: 34138966 PMCID: PMC8211150 DOI: 10.1371/journal.pone.0253489] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 06/06/2021] [Indexed: 12/24/2022] Open
Abstract
In the pursuit of suitable and effective solutions to SARS-CoV-2 infection, we investigated the efficacy of several phenolic compounds in controlling key cellular mechanisms involved in its infectivity. The way the SARS-CoV-2 virus infects the cell is a complex process and comprises four main stages: attachment to the cognate receptor, cellular entry, replication and cellular egress. Since, this is a multi-part process, it creates many opportunities to develop effective interventions. Targeting binding of the virus to the host receptor in order to prevent its entry has been of particular interest. Here, we provide experimental evidence that, among 56 tested polyphenols, including plant extracts, brazilin, theaflavin-3,3'-digallate, and curcumin displayed the highest binding with the receptor-binding domain of spike protein, inhibiting viral attachment to the human angiotensin-converting enzyme 2 receptor, and thus cellular entry of pseudo-typed SARS-CoV-2 virions. Both, theaflavin-3,3'-digallate at 25 μg/ml and curcumin above 10 μg/ml concentration, showed binding with the angiotensin-converting enzyme 2 receptor reducing at the same time its activity in both cell-free and cell-based assays. Our study also demonstrates that brazilin and theaflavin-3,3'-digallate, and to a still greater extent, curcumin, decrease the activity of transmembrane serine protease 2 both in cell-free and cell-based assays. Similar pattern was observed with cathepsin L, although only theaflavin-3,3'-digallate showed a modest diminution of cathepsin L expression at protein level. Finally, each of these three compounds moderately increased endosomal/lysosomal pH. In conclusion, this study demonstrates pleiotropic anti-SARS-CoV-2 efficacy of specific polyphenols and their prospects for further scientific and clinical investigations.
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Affiliation(s)
- Anna Goc
- Department of Infectious Diseases, Dr. Rath Research Institute, San Jose, California, United States of America
- * E-mail: (AN); (AG)
| | - Waldemar Sumera
- Department of Infectious Diseases, Dr. Rath Research Institute, San Jose, California, United States of America
| | - Matthias Rath
- Department of Infectious Diseases, Dr. Rath Research Institute, San Jose, California, United States of America
| | - Aleksandra Niedzwiecki
- Department of Infectious Diseases, Dr. Rath Research Institute, San Jose, California, United States of America
- * E-mail: (AN); (AG)
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41
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Merarchi M, Dudha N, Das BC, Garg M. Natural products and phytochemicals as potential anti-SARS-CoV-2 drugs. Phytother Res 2021; 35:5384-5396. [PMID: 34132421 PMCID: PMC8441929 DOI: 10.1002/ptr.7151] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 04/16/2021] [Accepted: 04/22/2021] [Indexed: 12/12/2022]
Abstract
The current pandemic responsible for the crippling of the health care system is caused by the novel SARS‐CoV‐2 in 2019 and leading to coronavirus disease 2019 (COVID‐19). The virus enters into humans by attachment of its Spike protein (S) to the ACE receptor present on the lung epithelial cell surface followed by cleavage of S protein by the cellular transmembrane serine protease (TMPRSS2). After entry, the SARS‐CoV‐2 RNA genome is released into the cytosol, where it highjacks host replication machinery for viral replication, assemblage, as well as the release of new viral particles. The major drug targets that have been identified for SARS‐CoV‐2 through host‐virus interaction studies include 3CLpro, PLpro, RNA‐dependent RNA polymerase, and S proteins. Several reports of natural compounds along with synthetic products have displayed promising results and some of them are Tripterygium wilfordii, Pudilan Xiaoyan Oral Liquid, Saponin derivates, Artemisia annua, Glycyrrhiza glabra L., Jinhua Qinggan granules, Xuebijing, and Propolis. This review attempts to disclose the natural products identified as anti‐SARS‐CoV‐2 based on in silico prediction and the effect of a variety of phytochemicals either alone and/or in combination with conventional treatments along with their possible molecular mechanisms involved for both prevention and treatment of the SARS‐CoV‐2 disease.
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Affiliation(s)
- Myriam Merarchi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Namrata Dudha
- Department of Biotechnology and Microbiology, School of Sciences, Noida International University, Gautam Budh Nagar, India
| | - Bhudev C Das
- Amity Institute of Molecular Medicine and Stem cell Research (AIMMSCR), Amity University Uttar Pradesh, Noida, India
| | - Manoj Garg
- Amity Institute of Molecular Medicine and Stem cell Research (AIMMSCR), Amity University Uttar Pradesh, Noida, India
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42
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Kandeil A, Mostafa A, Kutkat O, Moatasim Y, Al-Karmalawy AA, Rashad AA, Kayed AE, Kayed AE, El-Shesheny R, Kayali G, Ali MA. Bioactive Polyphenolic Compounds Showing Strong Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus 2. Pathogens 2021; 10:758. [PMID: 34203977 PMCID: PMC8232731 DOI: 10.3390/pathogens10060758] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 06/07/2021] [Accepted: 06/10/2021] [Indexed: 02/05/2023] Open
Abstract
Until now, there has been no direct evidence of the effectiveness of repurposed FDA-approved drugs against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections. Although curcumin, hesperidin, and quercetin have broad spectra of pharmacological properties, their antiviral activities against SARS-CoV-2 remain unclear. Our study aimed to assess the in vitro antiviral activities of curcumin, hesperidin, and quercetin against SARS-CoV-2 compared to hydroxychloroquine and determine their mode of action. In Vero E6 cells, these compounds significantly inhibited virus replication, mainly as virucidal agents primarily indicating their potential activity at the early stage of viral infection. To investigate the mechanism of action of the tested compounds, molecular docking studies were carried out against both SARS-CoV-2 spike (S) and main protease (Mpro) receptors. Collectively, the obtained in silico and in vitro findings suggest that the compounds could be promising SARS-CoV-2 Mpro inhibitors. We recommend further preclinical and clinical studies on the studied compounds to find a potential therapeutic targeting COVID-19 in the near future.
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Affiliation(s)
- Ahmed Kandeil
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (A.K.); (A.M.); (O.K.); (Y.M.); (A.E.K.); (R.E.-S.)
| | - Ahmed Mostafa
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (A.K.); (A.M.); (O.K.); (Y.M.); (A.E.K.); (R.E.-S.)
| | - Omnia Kutkat
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (A.K.); (A.M.); (O.K.); (Y.M.); (A.E.K.); (R.E.-S.)
| | - Yassmin Moatasim
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (A.K.); (A.M.); (O.K.); (Y.M.); (A.E.K.); (R.E.-S.)
| | - Ahmed A. Al-Karmalawy
- Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt;
| | - Adel A. Rashad
- Department of Biochemistry & Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA;
| | - Ahmed E. Kayed
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (A.K.); (A.M.); (O.K.); (Y.M.); (A.E.K.); (R.E.-S.)
| | - Azza E. Kayed
- Radiation Biology Department, Atomic Energy Authority, Cairo 13759, Egypt;
| | - Rabeh El-Shesheny
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (A.K.); (A.M.); (O.K.); (Y.M.); (A.E.K.); (R.E.-S.)
| | - Ghazi Kayali
- Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas, Houston, TX 77030, USA
- Human Link, Jewellery & Gemplex, Dubai 48800, United Arab Emirates
| | - Mohamed A. Ali
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; (A.K.); (A.M.); (O.K.); (Y.M.); (A.E.K.); (R.E.-S.)
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43
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Philip A, Ghiyasi R, Karppinen M. Photoactive Thin-Film Structures of Curcumin, TiO 2 and ZnO. Molecules 2021; 26:3214. [PMID: 34072008 PMCID: PMC8198897 DOI: 10.3390/molecules26113214] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 05/18/2021] [Accepted: 05/25/2021] [Indexed: 01/10/2023] Open
Abstract
Curcumin is known as a biologically active compound and a possible antimicrobial agent. Here, we combine it with TiO2 and ZnO semiconductors, known for their photocatalytic properties, with an eye towards synergistic photo-harvesting and/or antimicrobial effects. We deposit different nanoscale multi-layer structures of curcumin, TiO2 and ZnO, by combining the solution-based spin-coating (S-C) technique and the gas-phase atomic layer deposition (ALD) and molecular layer deposition (MLD) thin-film techniques. As one of the highlights, we demonstrate for these multi-layer structures a red-shift in the absorbance maximum and an expansion of the absorbance edge as far as the longest visible wavelength region, which activates them for the visible light harvesting. The novel fabrication approaches introduced here should be compatible with, e.g., textile substrates, opening up new horizons for novel applications such as new types of protective masks with thin conformal antimicrobial coatings.
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Affiliation(s)
| | | | - Maarit Karppinen
- Department of Chemistry and Materials Science, Aalto University, FI-00076 Espoo, Finland; (A.P.); (R.G.)
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44
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Tripathy S, Verma DK, Thakur M, Patel AR, Srivastav PP, Singh S, Chávez-González ML, Aguilar CN. Encapsulated Food Products as a Strategy to Strengthen Immunity Against COVID-19. Front Nutr 2021; 8:673174. [PMID: 34095193 PMCID: PMC8175800 DOI: 10.3389/fnut.2021.673174] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 04/26/2021] [Indexed: 12/18/2022] Open
Abstract
In December 2019, the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2)-a novel coronavirus was identified which was quickly distributed to more than 100 countries around the world. There are currently no approved treatments available but only a few preventive measures are available. Among them, maintaining strong immunity through the intake of functional foods is a sustainable solution to resist the virus attack. For this, bioactive compounds (BACs) are delivered safely inside the body through encapsulated food items. Encapsulated food products have benefits such as high stability and bioavailability, sustained release of functional compounds; inhibit the undesired interaction, and high antimicrobial and antioxidant activity. Several BACs such as ω-3 fatty acid, curcumin, vitamins, essential oils, antimicrobials, and probiotic bacteria can be encapsulated which exhibit immunological activity through different mechanisms. These encapsulated compounds can be recommended for use by various researchers, scientists, and industrial peoples to develop functional foods that can improve immunity to withstand the coronavirus disease 2019 (COVID-19) outbreak in the future. Encapsulated BACs, upon incorporation into food, offer increased functionality and facilitate their potential use as an immunity booster. This review paper aims to target various encapsulated food products and their role in improving the immunity system. The bioactive components like antioxidants, minerals, vitamins, polyphenols, omega (ω)-3 fatty acids, lycopene, probiotics, etc. which boost the immunity and may be a potential measure to prevent COVID-19 outbreak were comprehensively discussed. This article also highlights the potential mechanisms; a BAC undergoes, to improve the immune system.
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Affiliation(s)
- Soubhagya Tripathy
- Agricultural and Food Engineering Department, Indian Institute of Technology Kharagpur, Kharagpur, India
| | - Deepak Kumar Verma
- Agricultural and Food Engineering Department, Indian Institute of Technology Kharagpur, Kharagpur, India
| | - Mamta Thakur
- Department of Food Engineering and Technology, Sant Longowal Institute of Engineering and Technology, Longowal, India
| | - Ami R. Patel
- Division of Dairy and Food Microbiology, Mansinhbhai Institute of Dairy and Food Technology, Mehsana, India
| | - Prem Prakash Srivastav
- Agricultural and Food Engineering Department, Indian Institute of Technology Kharagpur, Kharagpur, India
| | - Smita Singh
- Department of Life Sciences (Food Technology), Graphic Era (Deemed to Be) University, Dehradun, India
| | - Mónica L. Chávez-González
- Bioprocesses Research Group, Food Research Department, School of Chemistry, Universidad Autonoma de Coahuila, Unidad Saltillo, Saltillo, Mexico
| | - Cristobal N. Aguilar
- Bioprocesses Research Group, Food Research Department, School of Chemistry, Universidad Autonoma de Coahuila, Unidad Saltillo, Saltillo, Mexico
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45
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Singh NA, Kumar P, Jyoti, Kumar N. Spices and herbs: Potential antiviral preventives and immunity boosters during COVID-19. Phytother Res 2021; 35:2745-2757. [PMID: 33511704 PMCID: PMC8013177 DOI: 10.1002/ptr.7019] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 12/03/2020] [Accepted: 01/03/2021] [Indexed: 01/08/2023]
Abstract
A severe acute respiratory syndrome is an unusual type of contagious pneumonia that is caused by SARS coronavirus. At present, the whole world is trying to combat this coronavirus disease and scientific communities are putting rigorous efforts to develop vaccines. However, there are only a few specific medical treatments for SARS-CoV-2. Apart from other public health measures taken to prevent this virus, we can boost our immunity with natural products. In this article, we have highlighted the potential of common spices and herbs as antiviral agents and immunity boosters. A questionnaire-based online survey has been conducted on home remedies during COVID-19 among a wide range of peoples (n-531) of different age groups (13-68 years) from various countries. According to the survey, 71.8% of people are taking kadha for combating infection and boosting immunity. Most people (86.1%) think that there is no side effect of kadha while 13.9% think vice versa. A total of 93.6% of people think that spices are helpful in curing coronavirus or other viral infection as well as boosting immunity. Most people are using tulsi drops, vitamin C, and chyawanprash for boosting their immunity. Therefore, we conclude from the survey and available literature that spices and herbs play a significant role against viral infections.
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Affiliation(s)
| | - Pradeep Kumar
- Department of ForestryNorth Eastern Regional Institute of Science and TechnologyNirjuliIndia
| | - Jyoti
- Department of MicrobiologyMohanlal Sukhadia UniversityUdaipurIndia
| | - Naresh Kumar
- Dairy Microbiology DivisionNational Dairy Research Institute, ICARKarnalIndia
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Nabila N, Hassan SR, Larasati GP, Yohan B, Sasmono RT, Adi AC, Iskandar F, Rachmawati H. The Influence of Surface Charge on the Antiviral Effect of Curcumin Loaded in Nanocarrier System. Pharm Nanotechnol 2021; 9:210-216. [PMID: 33563189 DOI: 10.2174/2211738509666210204121258] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 12/17/2020] [Accepted: 12/28/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Curcumin is a well-documented bioactive compound present in Curcuma sp., a tropical, medicinal plant. This substance exhibits broad-spectrum biological activities, including antivirus. Despite the lack of pharmaceutical properties of curcumin limits its clinical use. OBJECTIVE This study aims to produce curcumin nanoemulsion with different surface charge (curcumin (+) nanoemulsion and curcumin (-) nanoemulsion) and to evaluate its physical characteristics, in vitro cell cytotoxicity, and antiviral activity against dengue virus (DENV) 1 and 2. METHODS Two forms of nanoemulsion were prepared, which were differed from their surface charge through spontaneous procedure resulting in similar characteristics except for the zeta potential value. Cytotoxicity was determined using the RT-PCR method in the A549 cell line, and anti- DENV properties were determined by calculation of inhibitory concentration 50 (IC50) value. RESULTS The positive charge of curcumin-loaded nanoemulsion showed a better effect in reducing the viral replication represented by a lower IC50 value. In addition, DENV-1 was more sensitive and responsive to curcumin as compared to DENV-2. CONCLUSION Positive surface charge of curcumin-loaded nanoemulsion improves the antiviral effect of the curcumin, suggesting a promising approach for alternative treatment for dengue virus infection.
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Affiliation(s)
- Najwa Nabila
- School of Pharmacy, Bandung Institute of Technology, Ganesa 10, Bandung, 40132, Indonesia
| | - Siti R Hassan
- School of Pharmacy, Bandung Institute of Technology, Ganesa 10, Bandung, 40132, Indonesia
| | - Gladys P Larasati
- School of Pharmacy, Bandung Institute of Technology, Ganesa 10, Bandung, 40132, Indonesia
| | - Benediktus Yohan
- Eijkman Institute for Molecular Biology, Ministry of Research, Technology, and Higher Education, Diponegoro 69 Jakarta 10430, Indonesia
| | - R T Sasmono
- Eijkman Institute for Molecular Biology, Ministry of Research, Technology, and Higher Education, Diponegoro 69 Jakarta 10430, Indonesia
| | - Annis C Adi
- Department of Nutrition, Faculty of Public Health, University of Airlangga, Mulyorejo, Surabaya, 60115, Indonesia
| | - Ferry Iskandar
- Research Center for Nanosciences and Nanotechnology, Bandung Institute of Technology, Ganesa 10, Bandung, 40132, Indonesia
| | - Heni Rachmawati
- School of Pharmacy, Bandung Institute of Technology, Ganesa 10, Bandung, 40132, Indonesia
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Thimmulappa RK, Mudnakudu-Nagaraju KK, Shivamallu C, Subramaniam K, Radhakrishnan A, Bhojraj S, Kuppusamy G. Antiviral and immunomodulatory activity of curcumin: A case for prophylactic therapy for COVID-19. Heliyon 2021; 7:e06350. [PMID: 33655086 PMCID: PMC7899028 DOI: 10.1016/j.heliyon.2021.e06350] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 12/02/2020] [Accepted: 02/19/2021] [Indexed: 12/15/2022] Open
Abstract
Coronavirus disease-19 (COVID-19), a devastating respiratory illness caused by SARS-associated coronavirus-2 (SARS-CoV-2), has already affected over 64 million people and caused 1.48 million deaths, just 12 months from the first diagnosis. COVID-19 patients develop serious complications, including severe pneumonia, acute respiratory distress syndrome (ARDS), and or multiorgan failure due to exaggerated host immune response following infection. Currently, drugs that were effective against SARS-CoV are being repurposed for SARS-CoV-2. During this public health emergency, food nutraceuticals could be promising prophylactic therapeutics for COVID-19. Curcumin, a bioactive compound in turmeric, exerts diverse pharmacological activities and is widely used in foods and traditional medicines. This review presents several lines of evidence, which suggest curcumin as a promising prophylactic, therapeutic candidate for COVID-19. First, curcumin exerts antiviral activity against many types of enveloped viruses, including SARS-CoV-2, by multiple mechanisms: direct interaction with viral membrane proteins; disruption of the viral envelope; inhibition of viral proteases; induce host antiviral responses. Second, curcumin protects from lethal pneumonia and ARDS via targeting NF-κB, inflammasome, IL-6 trans signal, and HMGB1 pathways. Third, curcumin is safe and well-tolerated in both healthy and diseased human subjects. In conclusion, accumulated evidence indicates that curcumin may be a potential prophylactic therapeutic for COVID-19 in the clinic and public health settings.
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Affiliation(s)
- Rajesh K. Thimmulappa
- Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research, Mysore, India
| | - Kiran Kumar Mudnakudu-Nagaraju
- Department of Biotechnology and Bioinformatics, Faculty of Life Sciences, JSS Academy of Higher Education & Research, Mysore, India
| | - Chandan Shivamallu
- Department of Biotechnology and Bioinformatics, Faculty of Life Sciences, JSS Academy of Higher Education & Research, Mysore, India
| | - K.J.Thirumalai Subramaniam
- Centre of Excellence in Nanoscience & Technology, Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India
| | - Arun Radhakrishnan
- Centre of Excellence in Nanoscience & Technology, Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India
| | | | - Gowthamarajan Kuppusamy
- Centre of Excellence in Nanoscience & Technology, Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India
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Celik C, Gencay A, Ocsoy I. Can food and food supplements be deployed in the fight against the COVID 19 pandemic? Biochim Biophys Acta Gen Subj 2021; 1865:129801. [PMID: 33238195 PMCID: PMC7680693 DOI: 10.1016/j.bbagen.2020.129801] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 11/20/2020] [Accepted: 11/20/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Due to lack of approved drugs and vaccines, the medical world has resorted to older drugs, produced for viral infections and other diseases, as a remedy to combat COVID-19. The accumulating evidence from in vitro and in vivo studies for SARS-CoV and MERS-CoV have demonstrated that several polyphenols found in plants and zinc- polyphenol clusters have been in use as herbal medicines have antiviral activities against viruses with various mechanisms. SCOPE OF REVIEW Curcumin, zinc and zinc-ionophores have been considered as nutraceuticals and nutrients showing great antiviral activities with their medicinal like activities. MAJOR CONCLUSIONS In this work, we discussed the potential prophylactic and/or therapeutic effects of curcumin, zinc and zinc-ionophores in treatment of viral infections including COVID-19. GENERAL SIGNIFICANCE Curcuminoids and Zinc classified as nutraceuticals under GRAS (Generally Recognized As Safe) by FDA can provide complementary treatment for COVID 19 patients with their immunity-boosting and antiviral properties.
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Affiliation(s)
- Cagla Celik
- Department of Analytical Chemistry, Faculty of Pharmacy, Erciyes University, 38039 Kayseri, Turkey
| | - Ayse Gencay
- Department of Virology, Faculty of Veterinary, Erciyes University, 38039 Kayseri, Turkey
| | - Ismail Ocsoy
- Department of Analytical Chemistry, Faculty of Pharmacy, Erciyes University, 38039 Kayseri, Turkey.
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Šudomová M, Hassan STS. Nutraceutical Curcumin with Promising Protection against Herpesvirus Infections and Their Associated Inflammation: Mechanisms and Pathways. Microorganisms 2021; 9:microorganisms9020292. [PMID: 33572685 PMCID: PMC7912164 DOI: 10.3390/microorganisms9020292] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/27/2021] [Accepted: 01/28/2021] [Indexed: 12/15/2022] Open
Abstract
Herpesviruses are DNA viruses that infect humans and animals with the ability to induce latent and lytic infections in their hosts, causing critical health complications. The enrolment of nutraceutical anti-herpesvirus drugs in clinical investigations with promising levels of reduced resistance, free or minimal cellular toxicity, and diverse mechanisms of action might be an effective way to defeat challenges that hurdle the progress of anti-herpesvirus drug development, including the problems with drug resistance and recurrent infections. Therefore, in this review, we aim to hunt down all investigations that feature the curative properties of curcumin, a principal bioactive phenolic compound of the spice turmeric, in regard to various human and animal herpesvirus infections and inflammation connected with these diseases. Curcumin was explored with potent antiherpetic actions against herpes simplex virus type 1 and type 2, human cytomegalovirus, Kaposi’s sarcoma-associated herpesvirus, Epstein–Barr virus, bovine herpesvirus 1, and pseudorabies virus. The mechanisms and pathways by which curcumin inhibits anti-herpesvirus activities by targeting multiple steps in herpesvirus life/infectious cycle are emphasized. Improved strategies to overcome bioavailability challenges that limit its use in clinical practice, along with approaches and new directions to enhance the anti-herpesvirus efficacy of this compound, are also reviewed. According to the reviewed studies, this paper presents curcumin as a promising natural drug for the prevention and treatment of herpesvirus infections and their associated inflammatory diseases.
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Affiliation(s)
- Miroslava Šudomová
- Museum of Literature in Moravia, Klášter 1, 66461 Rajhrad, Czech Republic;
| | - Sherif T. S. Hassan
- Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 6-Suchdol, 16500 Prague, Czech Republic
- Correspondence: ; Tel.: +420-774-630-604
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