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Liu T, Li S, Wang X, Liu M, Wang Y, Ying J, Zhang S, Lin Y, Wang N, Bai Y, Xie L, Chen T, Feng Q, Xu X. Deciphering the therapeutic effects of Xiyanping injection: insights into pulmonary and gut microbiome modulation, SerpinB2/PAI-2 targeting, and alleviation of influenza a virus-induced lung injury. Virol J 2025; 22:19. [PMID: 39875956 PMCID: PMC11776135 DOI: 10.1186/s12985-025-02636-7] [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: 10/09/2024] [Accepted: 01/19/2025] [Indexed: 01/30/2025] Open
Abstract
Infection with Influenza A virus (IAV) induces severe inflammatory responses and lung injury, contributing significantly to mortality and morbidity rates. Alterations in the microbial composition of the lungs and intestinal tract resulting from infection could influence disease progression and treatment outcomes. Xiyanping (XYP) injection has demonstrated efficacy in clinical treatment across various viral infections. However, its specific effects and mechanisms against IAV remain unclear. In this study, we established an IAV infection mice model, and utilized 16 S rRNA sequencing, RNA sequencing, protein chips, and molecular docking, to investigate the mechanisms of XYP injection on altering pulmonary and gut microbiota, and identifying its target sites. We revealed that XYP injection significantly reduced mortality, weight loss, lung viral titers, and lung pathology in IAV-infected mice. XYP injection down-regulated the activity of malondialdehyde, and the levels of interleukin (IL)-1β, IL-5, IL-6, tumor necrosis factor-α, IL-18, IL-15, granulocyte colony-stimulating factor, IL-9, chemokine (C-C motif) ligand-5, and C-X-C motif chemokine ligand 5, while up-regulated the activities of glutathione peroxidase reactive and superoxide dismutase, and the level of interferon-γ. The diversity of the pulmonary and gut microbiota was altered slightly after XYP injection. The linear discriminant analysis of the gut microbes revealed a higher proportion of potentially beneficial bacteria, including Akkermansia, Parabacteroides goldsteinii, Defluviitaleaceae, Oscillospirales, and Eubacterium_coprostanoligenes_group characterized the XYP group. Peritoneal macrophage RNA sequencing highlighted Serpinb2 as the most significantly regulated gene by XYP injection, along with consistent changes in multiple downstream Th2 structure genes. KEGG pathway analysis indicated significant modifications in genes associated with influenza A, mitogen-activated protein kinase signaling, nuclear factor kappa-B signaling, and apoptosis following XYP injection. Finally, human protein chips and molecular docking were carried out to confirm the binding of the main component of XYP injection, andrographolide, with SERPINB2/PAI-2 protein. Overall, our study provides valuable insights into the therapeutic potential of XYP injection in treating influenza, highlighting its multifaceted effects on host microbiota and immune responses, and pinpointing SerpinB2/PAI-2 as the target for XYP injection in exerting anti-inflammatory and antiviral therapeutic mechanisms.
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Affiliation(s)
- Tengwen Liu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Shuping Li
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
- Beijing Institute of Chinese Medicine, Beijing, 100010, China
| | - Xuerui Wang
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
- Beijing Institute of Chinese Medicine, Beijing, 100010, China
- Beijing Key Laboratory of Innovative Research on Removing Stasis and Detoxification Theory in Infectious Diseases, Beijing, 100010, China
- Laboratory of Clinical Medicine, Capital Medical University, Beijing, 100010, China
| | - Mingjiang Liu
- College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China
| | - Yuchen Wang
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Jie Ying
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
| | - Shuwen Zhang
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
| | - Yan Lin
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
- Beijing Institute of Chinese Medicine, Beijing, 100010, China
| | - Ning Wang
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
- Beijing Institute of Chinese Medicine, Beijing, 100010, China
| | - Yungjing Bai
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
- Beijing Institute of Chinese Medicine, Beijing, 100010, China
- Beijing Key Laboratory of Innovative Research on Removing Stasis and Detoxification Theory in Infectious Diseases, Beijing, 100010, China
| | - Lan Xie
- Medical Systems Biology Research Center, Tsinghua University, Beijing, 100084, China
| | - Tengfei Chen
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China.
- Beijing Key Laboratory of Innovative Research on Removing Stasis and Detoxification Theory in Infectious Diseases, Beijing, 100010, China.
| | - Quansheng Feng
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
| | - Xiaolong Xu
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China.
- Beijing Institute of Chinese Medicine, Beijing, 100010, China.
- Beijing Key Laboratory of Innovative Research on Removing Stasis and Detoxification Theory in Infectious Diseases, Beijing, 100010, China.
- Laboratory of Clinical Medicine, Capital Medical University, Beijing, 100010, China.
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Kumar S, Ratha KK, Jaiswal S, Rao MM, Acharya R. Exploring the potential of andrographis paniculata and its bioactive compounds in the management of liver diseases: A comprehensive food chemistry perspective. FOOD CHEMISTRY ADVANCES 2024; 4:100674. [DOI: 10.1016/j.focha.2024.100674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Siridechakorn I, Bhattarakosol P, Sasivimolrattana T, Anoma S, Wongwad E, Nuengchamnong N, Kowitdamrong E, Boonyasuppayakorn S, Waranuch N. Inhibitory efficiency of Andrographis paniculata extract on viral multiplication and nitric oxide production. Sci Rep 2023; 13:19738. [PMID: 37957171 PMCID: PMC10643440 DOI: 10.1038/s41598-023-46249-y] [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: 10/25/2022] [Accepted: 10/30/2023] [Indexed: 11/15/2023] Open
Abstract
Andrographis paniculata (Burm. F.) Nees is a medicinal plant previously reported with broad-spectrum antivirals but the mode of inhibition remains elusive. The objective of this study was to identify the most active fraction from A. paniculata ethanol extract (APE, APE-2A, APE-2B and APE-2C) and dry powder extract (APSP) against influenza A (H3N2), representing RNA viruses, and herpes simplex virus-1 (HSV-1), representing DNA viruses. The results showed that the fractions APSP, APE, APE-2B, and APE-2C directly neutralized the HSV-1 and influenza A (H3N2) when incubated at room temperature for 60 min before infecting the cells. The results also showed that the additional APE-2A fraction also directly neutralized the influenza A (H3N2), but not the HSV-1. The APE, APE-2B and APE-2C inhibited the HSV-1 by more than 0.5 log when the fractions were introduced after infection. Similarly, the APSP and APE inhibited the influenza A (H3N2) more than 0.5 log after infection. Only 50 μg/mL APE-2C inhibited the viruses greater than 0.5 log. In addition, A. paniculata extracts were also evaluated for their interfering capacities against nitric oxide (NO) production in LPS-activated RAW 264.7 macrophages. As well, APE-2C potently inhibited NO production at the IC50 of 6.08 μg/mL. HPLC and LC-MS analysis indicated that the most actively antiviral fractions did not contain any andrographolide derivatives, whereas the andrographolide-rich fractions showed moderate activity.
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Affiliation(s)
- Ittipon Siridechakorn
- Cosmetics and Natural Products Research Center, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, 65000, Thailand
| | - Parvapan Bhattarakosol
- Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand.
| | - Thanayod Sasivimolrattana
- Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand
| | - Sasiprapa Anoma
- Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand
| | - Eakkaluk Wongwad
- Department of Cosmetic Sciences, School of Pharmaceutical Sciences, University of Phayao, Phayao, 56000, Thailand
| | - Nitra Nuengchamnong
- Faculty of Science, Science Laboratory Centre, Naresuan University, Phitsanulok, 65000, Thailand
| | - Ekasit Kowitdamrong
- Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand
| | - Siwaporn Boonyasuppayakorn
- Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand
| | - Neti Waranuch
- Cosmetics and Natural Products Research Center, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, 65000, Thailand.
- Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, 65000, Thailand.
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Thakur M, Singh M, Kumar S, Dwivedi VP, Dakal TC, Yadav V. A Reappraisal of the Antiviral Properties of and Immune Regulation through Dietary Phytochemicals. ACS Pharmacol Transl Sci 2023; 6:1600-1615. [PMID: 37974620 PMCID: PMC10644413 DOI: 10.1021/acsptsci.3c00178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Indexed: 11/19/2023]
Abstract
In the present era of the COVID-19 pandemic, viral infections remain a major cause of morbidity and mortality worldwide. In this day and age, viral infections are rampant and spreading rapidly. Among the most aggressive viral infections are ebola, AIDS (acquired immunodeficiency syndrome), influenza, and SARS (severe acute respiratory syndrome). Even though there are few treatment options for viral diseases, most of the antiviral therapies are ineffective owing to frequent mutations, the development of more aggressive strains, drug resistance, and possible side effects. Traditionally, herbal remedies have been used by healers, including for dietary and medicinal purposes. Many clinical and scientific studies have demonstrated the therapeutic potential of plant-derived natural compounds. Because of unsafe practices like blood transfusions and organ transplants from infected patients, medical supply contamination. Our antiviral therapies cannot achieve sterile immunity, and we have yet to find a cure for these pernicious infections. Herbs have been shown to improve therapeutic efficacy against a wide variety of viral diseases because of their high concentration of immunomodulatory phytochemicals (both immunoinhibitory and anti-inflammatory). Combined with biotechnology, this folk medicine system can lead to the development of novel antiviral drugs and therapies. In this Review, we will summarize some selected bioactive compounds with probable mechanisms of their antiviral actions, focusing on the immunological axis of these compounds.
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Affiliation(s)
- Mony Thakur
- Department
of Microbiology, Central University of Haryana, Mahendergarh, Haryana 123031, India
| | - Mona Singh
- Department
of Obstetrics and Gynaecology, Medical College
of Wisconsin, Milwaukee, Wisconsin 53226, United States
| | - Sandeep Kumar
- Division
of Cell Biology and Immunology, Council
of Scientific and Industrial Research - Institute of Microbial Technology, Chandigarh 160036, India
| | - Ved Prakash Dwivedi
- International
Centre for Genetic Engineering and Biotechnology, ICGEB Campus, Aruna Asaf Ali Marg, New Delhi 110067, India
| | - Tikam Chand Dakal
- Genome
and Computational Biology Lab, Department of Biotechnology, Mohanlal Sukhadia University, Udaipur, Rajasthan 313001, India
| | - Vinod Yadav
- Department
of Microbiology, Central University of Haryana, Mahendergarh, Haryana 123031, India
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Li J, Guo S, Tan Y, Zhang J, Wu Z, Stalin A, Zhang F, Huang Z, Wu C, Liu X, Huang J, Wu J. Integrated network pharmacology analysis and in vitro validation revealed the underlying mechanism of Xiyanping injection in treating coronavirus disease 2019. Medicine (Baltimore) 2023; 102:e34866. [PMID: 37653800 PMCID: PMC10470725 DOI: 10.1097/md.0000000000034866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 07/28/2023] [Accepted: 07/31/2023] [Indexed: 09/02/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, leading to a pandemic. In China, Xiyanping injection (XYP) has been recommended as a drug for COVID-19 treatment in the Guideline on Diagnosis and Treatment of COVID-19 by the National Health Commission of the People Republic of China and National Administration of Traditional Chinese Medicine (Trial eighth Edition). However, the relevant mechanisms at the molecular-level need to be further elucidated. METHODS In this study, XYP related active ingredients, potential targets and COVID-19 related genes were searched in public databases. Protein-protein interaction network and module analyzes were used to screen for key targets. gene ontology and Kyoto encyclopedia of genes and genomes were performed to investigate the potentially relevant signaling pathways. Molecular docking was performed using Autodock Tools and Vina. For the validation of potential mechanism, PolyI:C was used to induce human lung epithelial cells for an inflammation model. Subsequently, CCK-8 assays, enzyme-linked immunosorbent assay, reverse transcription quantitative polymerase chain reaction and western blot were employed to determine the effect of XYP on the expression of key genes. RESULTS Seven effective active ingredients in XYP were searched for 123 targets in the relevant databases. Furthermore, 6446 COVID-19 disease targets were identified. Sodium 9-dehydro-17-hydro-andrographolide-19-yl sulfate was identified as the vital active compounds, and IL-6, TNF, IL-1β, CXCL8, STAT3, MAPK1, MAPK14, and MAPK8 were considered as the key targets. In addition, molecular docking revealed that the active compound and the targets showed good binding affinities. The enrichment analysis predicted that the XYP could regulate the IL-17, Toll-like receptor, PI3K-Akt and JAK-STAT signaling pathways. Consistently, further in vitro experiments demonstrated that XYP could slow down the cytokine storm in the lung tissue of COVID-19 patients by down-regulating IL-6, TNF-α, IL-1β, CXCL8, and p-STAT3. CONCLUSION Through effective network pharmacology analysis and molecular docking, this study suggests that XYP contains many effective compounds that may target COVID-19 related signaling pathways. Moreover, the in vitro experiment confirmed that XYP could inhibit the cytokine storm by regulating genes or proteins related to immune and inflammatory responses.
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Affiliation(s)
- Jialin Li
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
- College of Pharmacy, Harbin Medical University-Daqing, Daqing, China
| | - Siyu Guo
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Yingying Tan
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Jingyuan Zhang
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Zhishan Wu
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Antony Stalin
- Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, China
| | - Fanqin Zhang
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Zhihong Huang
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Chao Wu
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Xinkui Liu
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Jiaqi Huang
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Jiarui Wu
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
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Diantini A, Febriyanti RM, Levita J. Efficacy and Safety of Add-On Plant-Based Drugs for COVID-19 Patients: A Review of the Randomized Control Trials. Infect Drug Resist 2023; 16:3879-3891. [PMID: 37361940 PMCID: PMC10289101 DOI: 10.2147/idr.s417727] [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: 04/18/2023] [Accepted: 06/13/2023] [Indexed: 06/28/2023] Open
Abstract
COVID-19 caused by the infection of SARS-CoV-2 is still a global concern. WHO reported that from 13 March to 9 April 2023, there were 3 million new cases and approximately 23,000 deaths, mostly occurring in the South-East Asia and Eastern Mediterranean regions, which is predicted due to the new Omicron variant, Arcturus XBB.1.16. Many studies have reported the potency of medicinal plants in enhancing the function of the immune system to combat virus infection. The literature review aimed to describe the efficacy and safety of add-on plant-based drugs for COVID-19 patients. The articles were explored on the PubMed and Cochrane Library databases, and published during 2020-2023. Twenty-two varieties of plants were used as add-on therapy for COVID-19 patients. These plants were Andrographis paniculata, Viola odorata, Withania somnifera, Zingiber officinale, Curcuma longa, Ferula foetida, Centella asiatica, Thymus vulgaris, Citrus sinensis, Eugenia caryophyllus, Boswellia carterii, Elettaria cardamomum, Salvia rosmarinus, Piper nigrum, Alstonia scholaris, Picrorhiza kurroa, Swertia chirata, Caesalpinia crista, Cucurbita maxima, Tinospora cordifolia, Ocimum sanctum, and Allium sativum. The best efficacy of an add-on therapy for COVID-19 patients was found in A. paniculata herbs as a single component in pharmaceutical dosage form or in combination with other plants. The safety of the plant has been confirmed. A. paniculata does not show interaction with remdesivir or favipiravir, however, caution and therapy drug monitoring is needed if A. paniculata is used in combination with lopinavir or ritonavir because a strong noncompetitive inhibition of CYP3A4 may occur.
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Affiliation(s)
- Ajeng Diantini
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 46363, Indonesia
| | - R Maya Febriyanti
- Department of Biology Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 46363, Indonesia
| | - Jutti Levita
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 46363, Indonesia
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Qin X, Wang X, Tian M, Dong Z, Wang J, Wang C, Huang Q. The role of Andrographolide in the prevention and treatment of liver diseases. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 109:154537. [PMID: 36610122 DOI: 10.1016/j.phymed.2022.154537] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 10/12/2022] [Accepted: 11/01/2022] [Indexed: 06/17/2023]
Abstract
BACKGROUND The presence or absence of damage to the liver organ is crucial to a person's health. Nutritional disorders, alcohol consumption, and drug abuse are the main causes of liver disease. Liver transplantation is the last irrevocable option for liver disease and has become a serious economic burden worldwide. Andrographolide (AP) is one of the main active ingredients of Herba Andrographitis. It has several biological activities and has been reported to have protective and therapeutic effects against liver diseases. Earlier literature has been written on AP's role in treating inflammation and other diseases, and there has not been a systematic review on liver diseases. This review is dedicated to sorting out the research results of AP against liver diseases. Pharmacokinetics, toxicity, and nanotechnology to improve bioavailability are discussed. Finally, an outlook and assessment of its future are provided. METHODS Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed and web of Science databases were used to search all relevant literature on AP for liver disease up to 2022. RESULTS Studies have shown that AP plays an important role in different liver disease phenotypes, mainly through anti-inflammatory and antioxidant activities. AP regulates HO-1 and inhibits hepatitis virus replication. It affects the NF-κB pathway, downregulates inflammatory factors such as IL-1β, IL-6, and TNF-α, and reduces liver damage. In preventing liver fibrosis, AP inhibits angiogenesis and activation of hepatic stellate cells and reduces oxidative stress involved in the Nrf2 and TGF-β1/Smad pathways. In addition, AP impedes the development of liver cancer by promoting apoptosis and autonomous phagocytosis in a cell-dependent way. Interestingly, miRNAs are involved in the therapeutic process of liver cancer and hepatic fibrosis. The poor solubility of AP limits the development of dosage forms. Therefore, the advent of nanoformulations has improved bioavailability. Although the effect of AP is dose- and time-dependent, the magnitude of its toxicity is not negligible. Some clinical trials have shown that AP has mild side effects. CONCLUSIONS AP, as an effective natural product, has a good effect on the liver disease through multiple pathways and targets. However, the dose reaches a certain level, leading to its toxicity and side effects. For better clinical application of AP, high-quality clinical and toxic intervention mechanisms are needed to validate current studies. In addition, modulation of miRNA-mediated hepatocellular carcinoma and liver fibrosis and synergistic action with drugs may be the future focus of AP. In conclusion, AP can be regarded as an important candidate for treating different liver diseases in the future.
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Affiliation(s)
- Xiaoyan Qin
- State Key Laboratory of Southwestern Chinese Medicine Resources, No.1166, Liutai Road, Wenjiang District, Chengdu, 611137, PR. China; College of Pharmacy, Chengdu University of Traditional Chinese Medicine, No.1166, Liutai Road, Wenjiang District, Chengdu, 611137, PR. China
| | - Xi Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, No.1166, Liutai Road, Wenjiang District, Chengdu, 611137, PR. China; College of Pharmacy, Chengdu University of Traditional Chinese Medicine, No.1166, Liutai Road, Wenjiang District, Chengdu, 611137, PR. China
| | - Maoying Tian
- State Key Laboratory of Southwestern Chinese Medicine Resources, No.1166, Liutai Road, Wenjiang District, Chengdu, 611137, PR. China; College of Pharmacy, Chengdu University of Traditional Chinese Medicine, No.1166, Liutai Road, Wenjiang District, Chengdu, 611137, PR. China
| | - Zhaowei Dong
- State Key Laboratory of Southwestern Chinese Medicine Resources, No.1166, Liutai Road, Wenjiang District, Chengdu, 611137, PR. China; College of Pharmacy, Chengdu University of Traditional Chinese Medicine, No.1166, Liutai Road, Wenjiang District, Chengdu, 611137, PR. China
| | - Jin Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, No.1166, Liutai Road, Wenjiang District, Chengdu, 611137, PR. China; College of Pharmacy, Chengdu University of Traditional Chinese Medicine, No.1166, Liutai Road, Wenjiang District, Chengdu, 611137, PR. China
| | - Chao Wang
- Sichuan Integrated Traditional Chinese and Western Medicine Hospital, No.51, Section 4, Renmin South Road, Wuhou District, Chengdu, 610042, PR. China.
| | - Qinwan Huang
- State Key Laboratory of Southwestern Chinese Medicine Resources, No.1166, Liutai Road, Wenjiang District, Chengdu, 611137, PR. China; College of Pharmacy, Chengdu University of Traditional Chinese Medicine, No.1166, Liutai Road, Wenjiang District, Chengdu, 611137, PR. China.
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Discovery of dehydroandrographolide derivatives with C19 hindered ether as potent anti-ZIKV agents with inhibitory activities to MTase of ZIKV NS5. Eur J Med Chem 2022; 243:114710. [DOI: 10.1016/j.ejmech.2022.114710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 08/20/2022] [Accepted: 08/21/2022] [Indexed: 11/22/2022]
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Intharuksa A, Arunotayanun W, Yooin W, Sirisa-ard P. A Comprehensive Review of Andrographis paniculata (Burm. f.) Nees and Its Constituents as Potential Lead Compounds for COVID-19 Drug Discovery. Molecules 2022; 27:molecules27144479. [PMID: 35889352 PMCID: PMC9316804 DOI: 10.3390/molecules27144479] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 07/05/2022] [Accepted: 07/11/2022] [Indexed: 11/17/2022] Open
Abstract
The COVID-19 pandemic has intensively disrupted global health, economics, and well-being. Andrographis paniculata (Burm. f.) Nees has been used as a complementary treatment for COVID-19 in several Asian countries. This review aimed to summarize the information available regarding A. paniculata and its constituents, to provide critical points relating to its pharmacological properties, safety, and efficacy, revealing its potential to serve as a source of lead compounds for COVID-19 drug discovery. A. paniculata and its active compounds possess favorable antiviral, anti-inflammatory, immunomodulatory, and antipyretic activities that could be beneficial for COVID-19 treatment. Interestingly, recent in silico and in vitro studies have revealed that the active ingredients in A. paniculata showed promising activities against 3CLpro and its virus-specific target protein, human hACE2 protein; they also inhibit infectious virion production. Moreover, existing publications regarding randomized controlled trials demonstrated that the use of A. paniculata alone or in combination was superior to the placebo in reducing the severity of upper respiratory tract infection (URTI) manifestations, especially as part of early treatment, without serious side effects. Taken together, its chemical and biological properties, especially its antiviral activities against SARS-CoV-2, clinical trials on URTI, and the safety of A. paniculata, as discussed in this review, support the argument that A. paniculata is a promising natural source for drug discovery regarding COVID-19 post-infectious treatment, rather than prophylaxis.
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Affiliation(s)
- Aekkhaluck Intharuksa
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand; (A.I.); (W.Y.); (P.S.-a.)
| | - Warunya Arunotayanun
- Kanchanabhishek Institute of Medical and Public Health Technology, Praboromarajchanok Institute, Nonthaburi 11150, Thailand
- Correspondence:
| | - Wipawadee Yooin
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand; (A.I.); (W.Y.); (P.S.-a.)
| | - Panee Sirisa-ard
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand; (A.I.); (W.Y.); (P.S.-a.)
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Kamboj S, Rajput A, Rastogi A, Thakur A, Kumar M. Targeting non-structural proteins of Hepatitis C virus for predicting repurposed drugs using QSAR and machine learning approaches. Comput Struct Biotechnol J 2022; 20:3422-3438. [PMID: 35832613 PMCID: PMC9271984 DOI: 10.1016/j.csbj.2022.06.060] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 06/27/2022] [Accepted: 06/27/2022] [Indexed: 11/24/2022] Open
Abstract
Hepatitis C virus (HCV) infection causes viral hepatitis leading to hepatocellular carcinoma. Despite the clinical use of direct-acting antivirals (DAAs) still there is treatment failure in 5-10% cases. Therefore, it is crucial to develop new antivirals against HCV. In this endeavor, we developed the "Anti-HCV" platform using machine learning and quantitative structure-activity relationship (QSAR) approaches to predict repurposed drugs targeting HCV non-structural (NS) proteins. We retrieved experimentally validated small molecules from the ChEMBL database with bioactivity (IC50/EC50) against HCV NS3 (454), NS3/4A (495), NS5A (494) and NS5B (1671) proteins. These unique compounds were divided into training/testing and independent validation datasets. Relevant molecular descriptors and fingerprints were selected using a recursive feature elimination algorithm. Different machine learning techniques viz. support vector machine, k-nearest neighbour, artificial neural network, and random forest were used to develop the predictive models. We achieved Pearson's correlation coefficients from 0.80 to 0.92 during 10-fold cross validation and similar performance on independent datasets using the best developed models. The robustness and reliability of developed predictive models were also supported by applicability domain, chemical diversity and decoy datasets analyses. The "Anti-HCV" predictive models were used to identify potential repurposing drugs. Representative candidates were further validated by molecular docking which displayed high binding affinities. Hence, this study identified promising repurposed drugs viz. naftifine, butalbital (NS3), vinorelbine, epicriptine (NS3/4A), pipecuronium, trimethaphan (NS5A), olodaterol and vemurafenib (NS5B) etc. targeting HCV NS proteins. These potential repurposed drugs may prove useful in antiviral drug development against HCV.
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Affiliation(s)
- Sakshi Kamboj
- Virology Unit and Bioinformatics Centre, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Sector 39A, Chandigarh 160036, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Akanksha Rajput
- Virology Unit and Bioinformatics Centre, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Sector 39A, Chandigarh 160036, India
| | - Amber Rastogi
- Virology Unit and Bioinformatics Centre, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Sector 39A, Chandigarh 160036, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Anamika Thakur
- Virology Unit and Bioinformatics Centre, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Sector 39A, Chandigarh 160036, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Manoj Kumar
- Virology Unit and Bioinformatics Centre, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Sector 39A, Chandigarh 160036, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
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11
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Recent advancement in small molecules as HCV inhibitors. Bioorg Med Chem 2022; 60:116699. [PMID: 35278819 DOI: 10.1016/j.bmc.2022.116699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 02/18/2022] [Accepted: 03/02/2022] [Indexed: 11/24/2022]
Abstract
Hepatitis C virus (HCV) has caused a considerable threat to human health. To date, no treatments are without side effects. The proteins and RNA associated with HCV have specific functions during the viral life cycle. The vulnerabilities to virus are associated with those proteins or RNA. Thus, targeting these proteins and RNA is an efficient strategy to develop anti-HCV therapeutics. The treatment for HCV-infected patients has been greatly improved after the approval of direct-acting antivirals (DAAs). However, the cost of DAAs is unusually high, which adds to the economic burden on patients with chronic liver diseases. So far, many efforts have been devoted to the development of small molecules as novel HCV inhibitors. Investigations on the inhibitory activities of these small molecules have involved the target identification and the mechanism of action. In this mini-review, these small molecules divided into four kinds were elaborated, which focused on their targets and structural features. Furthermore, we raised the current challenges and promising prospects. This mini-review may facilitate the development of small molecules with improved activities targeting HCV based on the chemical scaffolds of HCV inhibitors.
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12
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Qu J, Liu Q, You G, Ye L, Jin Y, Kong L, Guo W, Xu Q, Sun Y. Advances in ameliorating inflammatory diseases and cancers by andrographolide: Pharmacokinetics, pharmacodynamics, and perspective. Med Res Rev 2021; 42:1147-1178. [PMID: 34877672 DOI: 10.1002/med.21873] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 07/07/2021] [Accepted: 11/10/2021] [Indexed: 12/26/2022]
Abstract
Andrographolide, a well-known natural lactone having a range of pharmacological actions in traditional Chinese medicine. It has long been used to cure a variety of ailments. In this review, we cover the pharmacokinetics and pharmacological activity of andrographolide which supports its further clinical application in cancers and inflammatory diseases. Growing evidence shows a good therapeutic effect in inflammatory diseases, including liver diseases, joint diseases, respiratory system diseases, nervous system diseases, heart diseases, inflammatory bowel diseases, and inflammatory skin diseases. As a result, the effects of andrographolide on immune cells and the processes that underpin them are discussed. The preclinical use of andrographolide to different organs in response to malignancies such as colorectal, liver, gastric, breast, prostate, lung, and oral cancers has also been reviewed. In addition, several clinical trials of andrographolide in inflammatory diseases and cancers have been summarized. This review highlights recent advances in ameliorating inflammatory diseases as well as cancers by andrographolide and its analogs, providing a new perspective for subsequent research of this traditional natural product.
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Affiliation(s)
- Jiao Qu
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Science, Nanjing University, Nanjing, China
| | - Qianqian Liu
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Science, Nanjing University, Nanjing, China
| | - Guoquan You
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Science, Nanjing University, Nanjing, China
| | - Ling Ye
- Biopharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China
| | - Yiguang Jin
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
| | - Lingdong Kong
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Science, Nanjing University, Nanjing, China
| | - Wenjie Guo
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Science, Nanjing University, Nanjing, China
| | - Qiang Xu
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Science, Nanjing University, Nanjing, China.,Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yang Sun
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Science, Nanjing University, Nanjing, China.,Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.,Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, China
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13
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Blumea lacera DC., accelerates the healing of acetic acid induced ulcerative colitis in rats by regulating oxidative stress and colonic inflammation: in-vivo and in silico molecular docking experiments. ADVANCES IN TRADITIONAL MEDICINE 2021. [DOI: 10.1007/s13596-020-00454-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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14
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Gupta S, Mishra KP, Gupta R, Singh SB. Andrographolide - A prospective remedy for chikungunya fever and viral arthritis. Int Immunopharmacol 2021; 99:108045. [PMID: 34435582 DOI: 10.1016/j.intimp.2021.108045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 08/01/2021] [Accepted: 08/01/2021] [Indexed: 12/14/2022]
Abstract
AIM Andrographolide, the major bioactive compound of the plant Andrographis paniculata, exerts anti-inflammatory, cyto-, neuro- and hepato-protective effects. Traditional remedies for infectious diseases include A. paniculata for maladies like fever, pain, rashes which are associated with chikungunya and other arboviral diseases. Since andrographolide and A. paniculata have potent antiviral properties, the present review aims to provide a comprehensive report of symptoms and immunological molecules involved in chikungunya virus (CHIKV) infection and the therapeutic role of andrographolide in the mitigation of chikungunya and associated symptoms. MATERIALS AND METHODS Studies on the therapeutic role of A. paniculata and andrographolide in chikungunya and other viral infections published between 1991 and 2021 were searched on various databases. RESULTS AND DISCUSSION The havoc created by chikungunya is due to the associated debilitating symptoms including arthralgia and myalgia which sometimes remains for years. The authors reviewed and summarized the various symptoms and immunological molecules related to CHIKV replication and associated inflammation, oxidative and unfolded protein stress, apoptosis and arthritis. Additionally, the authors suggested andrographolide as a remedy for chikungunya and other arboviral infections by highlighting its role in the regulation of molecules involved in unfolded protein response pathway, immunomodulation, inflammation, virus multiplication, oxidative stress, apoptosis and arthritis. CONCLUSION The present review demonstrated the major complications associated with chikungunya and the role of andrographolide in alleviating the chikungunya associated symptoms to encourage further investigations using this promising compound towards early development of an anti-CHIKV drug. Chemical Compound studied: andrographolide (PubChem CID: 5318517).
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Affiliation(s)
- Swati Gupta
- Division of Epidemiology and Communicable Diseases, Indian Council of Medical Research (ICMR), Ansari Nagar, New Delhi 110029, India.
| | - K P Mishra
- Defence Research and Development Organization (DRDO)-HQ, Rajaji Marg, New Delhi 110011, India
| | - Rupali Gupta
- Department of Neurology, Duke University Medical Center, Durham, NC, United States
| | - S B Singh
- National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
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15
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Abstract
Andrographolide is a labdane diterpenoid extracted and purified from the aerial parts of plants belonging to genus Andrographis (Acanthaceae). The research has shown the plant based compound is low cytotoxic, having antimicrobial, anti-cancer, antiviral and anti-parasitic effects. Andrographolide both prevent spread as well as transmission of virus to neighboring cells by interfering with different cell signaling pathways. In addition to its medicinal value, plant has been found having nutritional value. Therefore being cost effective, easy availability and having nutritional value as a natural supplement, can be used to improve the quality of life in countries having low standard of living. Due to the limited number of effective vaccines, the plant-based antiviral drugs have provided considerable hope for fighting against the viral infections. The plant-derived compound when produced in large quantities is cost effective with low cytotoxic effects. However, much deep insight research at the molecular level is needed to develop the molecules against the viral infection. This paper aims to highlight the antiviral role of Andrographolide that can made significant contributions toward the improvement of human health and will also summarize the current status and future strategies concerning the therapeutic applications of Andrographolide to combat different viral disease in humans.
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16
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Zhang X, Lv L, Zhou Y, Xie L, Xu Q, Zou X, Ding Y, Tian J, Fan J, Fan H, Yang Y, Ye X. Efficacy and safety of Xiyanping injection in the treatment of COVID-19: A multicenter, prospective, open-label and randomized controlled trial. Phytother Res 2021; 35:4401-4410. [PMID: 33979464 PMCID: PMC8242486 DOI: 10.1002/ptr.7141] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 03/17/2021] [Accepted: 04/11/2021] [Indexed: 01/23/2023]
Abstract
Xiyanping (XYP) is a Chinese herbal medicine used in the clinic to treat respiratory infection and pneumonia. Recent evidence identified XYP as a potential inhibitor of severe acute respiratory syndrome coronavirus 2, implying XYP as a possible treatment for the coronavirus disease 2019 (COVID-19). Here, we conducted a prospective, multicenter, open-label and randomized controlled trial to evaluate the safety and effectiveness of XYP injection in patients with mild to moderate COVID-19. We consecutively recruited 130 COVID-19 patients with mild to moderate symptoms from five study sites, and randomized them in 1:1 ratio to receive XYP injection in combination with standard therapy or receive standard supportive therapy alone. We found that XYP injection significantly reduced the time to cough relief, fever resolution and virus clearance. Less patients receiving XYP injection experienced disease progression to the severe stage during the treatment process. No severe adverse events were reported during the study. Taken together, XYP injection is safe and effective in improving the recovery of patients with mild to moderate COVID-19. However, further studies are warranted to evaluate the efficacy of XYP in an expanded cohort comprising COVID-19 patients at different disease stages.
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Affiliation(s)
- Xin‐Yi Zhang
- Department of Respiratory DiseasesThe Second Affiliated Hospital of Nanchang UniversityNanchangChina
| | - Lang Lv
- Department of Drug ResearchState Key Laboratory of Innovative Natural Medicine and TCM InjectionsGanzhouChina
| | - Yu‐Long Zhou
- Department of Respiratory DiseasesThe Ninth Hospital of NanchangNanchangChina
| | - Liang‐Dong Xie
- Department of Critical Care MedicineThe Fifth People's Hospital of GanzhouGanzhouChina
| | - Qin Xu
- Department of Respiratory DiseasesFengcheng People's HospitalFengchengChina
| | - Xiao‐Fan Zou
- Department of Respiratory DiseasesJi'an Central People's HospitalJi'anChina
| | - Yan Ding
- Department of Respiratory DiseasesThe First Affiliated Hospital of Gannan Medical UniversityGanzhouChina
| | - Jie Tian
- Department of Respiratory DiseasesThe Ninth Hospital of NanchangNanchangChina
| | - Jia‐Liang Fan
- Department of Respiratory DiseasesJi'an Central People's HospitalJi'anChina
| | - Hai‐Wei Fan
- Department of Drug ResearchState Key Laboratory of Innovative Natural Medicine and TCM InjectionsGanzhouChina
| | - Yi‐Xi Yang
- Department of Drug ResearchState Key Laboratory of Innovative Natural Medicine and TCM InjectionsGanzhouChina
| | - Xiao‐Qun Ye
- Department of Respiratory DiseasesThe Second Affiliated Hospital of Nanchang UniversityNanchangChina
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17
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Murugan NA, Pandian CJ, Jeyakanthan J. Computational investigation on Andrographis paniculata phytochemicals to evaluate their potency against SARS-CoV-2 in comparison to known antiviral compounds in drug trials. J Biomol Struct Dyn 2021; 39:4415-4426. [PMID: 32543978 PMCID: PMC7309306 DOI: 10.1080/07391102.2020.1777901] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 05/27/2020] [Indexed: 12/14/2022]
Abstract
The outbreak due to SARS-CoV-2 (or Covid-19) is spreading alarmingly and number of deaths due to infection is aggressively increasing every day. Due to the rapid human to human transmission of Covid-19, we are in need to find a potent drug at the earliest by ruling-out the traditional time-consuming approach of drug development. This is only possible if we use reliable computational approaches for screening compounds from chemical space or by drug repurposing or by finding the phytochemicals and nutraceuticals from plants as they can be immediately used without the need for carrying out drug-trials to test safety and efficacy. A number of plant products were routinely suggested as drugs in traditional Indian and Chinese medicine. Here using molecular docking approach, and combined molecular dynamics and MM-GBSA based free energy calculations approach, we study the potency of the four selected phytochemicals namely andrographolide (AGP1), 14-deoxy 11,12-didehydro andrographolide (AGP2), neoandrographolide (AGP3) and 14-deoxy andrographolide (AGP4) from A. paniculata plant against the four key targets including three non-structural proteins (3 L main protease (3CLpro), Papain-like proteinase (PLpro) and RNA-directed RNA polymerase (RdRp)) and a structural protein (spike protein (S)) of the virus which are responsible for replication, transcription and host cell recognition. The therapeutic potential of the selected phytochemicals against Covid-19 were also evaluated in comparison with a few commercially available drugs. The binding free energy data suggest that AGP3 could be used as a cost-effective drug-analog for treating covid-19 infection in developing countries.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Natarajan Arul Murugan
- Department of Theoretical Chemistry and Biology, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, Sweden
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18
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Prasanth DSNBK, Murahari M, Chandramohan V, Bhavya G, Lakshmana Rao A, Panda SP, Rao GSNK, Chakravarthi G, Teja N, Suguna Rani P, Ashu G, Purnadurganjali C, Akhil P, Vedita Bhavani G, Jaswitha T. In-silico strategies of some selected phytoconstituents from Melissa officinalis as SARS CoV-2 main protease and spike protein (COVID-19) inhibitors. MOLECULAR SIMULATION 2021. [PMCID: PMC7885731 DOI: 10.1080/08927022.2021.1880576] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Melissa officinalis (Lamiaceae) was used to treat multiple human afflictions. Literary works demonstrated that it has many biological activities. Today’s research aims to recognise Melissa officinalis phyto-derived anti-viral compounds against main protease and spike protein of COVID-19, to gain insight into the molecular interactions. In the current study, 12 molecules taken from Melissa officinalis were analysed through docking, which is derived from the PubMed database. Docking experiments were conducted with Autodock tool. AdmetSAR and Data warrior servers were eventually used for drug-like prediction. Our research shows that three phytoconstituents from Melissa officinalis, namely, Luteolin-7-glucoside-3′-glucuronide, Melitric acid-A and Quadranoside-III have exhibited better binding affinity and stability with the targets of COVID-19 main protease and spike protein. The identified substances can be further extended for in vitro and in vivo studies to assess their effectiveness against COVID-19.
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Affiliation(s)
- D. S. N. B. K. Prasanth
- Pharmacognosy Research Division, K L College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, India
| | - Manikanta Murahari
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bangalore, India
| | - Vivek Chandramohan
- Siddaganga Institute of Technology, Department of Biotechnology, Siddaganga Institute of Technology, Tumakuru, India
| | - Gangadharappa Bhavya
- Department of Biotechnology, M.S. Ramaiah Institute of Technology, Bangalore, India
| | - Atmakuri Lakshmana Rao
- Department of Pharmaceutical Analysis, V. V. Institute of Pharmaceutical Sciences, Gudlavalleru, India
| | - Siva Prasad Panda
- Pharmacognosy Research Division, K L College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, India
| | - G. S. N. Koteswara Rao
- Pharmaceutics Research Division, K L College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, India
| | - Guntupalli Chakravarthi
- Pharmacognosy Research Division, K L College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, India
| | - Nayudu Teja
- Department of Pharmaceutics, V. V. Institute of Pharmaceutical Sciences, Gudlavalleru, India
| | - Peddireddy Suguna Rani
- Sri Venkateswara University, Department of Pharmacology, Sri Venkateswara University, Tirupati, India
| | - Gummadi Ashu
- Department of Pharmaceutics, V. V. Institute of Pharmaceutical Sciences, Gudlavalleru, India
| | | | - Puvvala Akhil
- Department of Pharmaceutical Analysis, V. V. Institute of Pharmaceutical Sciences, Gudlavalleru, India
| | - Gorriputti Vedita Bhavani
- Department of Pharmaceutical Analysis, V. V. Institute of Pharmaceutical Sciences, Gudlavalleru, India
| | - Tirumalasetti Jaswitha
- Department of Pharmaceutical Analysis, V. V. Institute of Pharmaceutical Sciences, Gudlavalleru, India
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Satapathy P, Prakash JK, More SS, Chandramohan V, Zameer F. Structural modulation of dual oxidase (Duox) in Drosophila melanogaster by phyto-elicitors: A free energy study with molecular dynamics approach. INFORMATICS IN MEDICINE UNLOCKED 2021. [DOI: 10.1016/j.imu.2021.100811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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20
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Choudhary P, Bhowmik A, Chakdar H, Khan MA, Selvaraj C, Singh SK, Murugan K, Kumar S, Saxena AK. Understanding the biological role of PqqB in Pseudomonas stutzeri using molecular dynamics simulation approach. J Biomol Struct Dyn 2020; 40:4237-4249. [PMID: 33287678 DOI: 10.1080/07391102.2020.1854860] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Phosphate solubilization is an important and widely studied plant growth promoting trait exhibited by many bacteria. Pyrroloquinoline quinone (PQQ), a redox cofactor of methanol and glucose dehydrogenases has been well established as essential for phosphate solubilization. PQQ operon has been well studied in growth promoting rhizobacteria like Pseudomonas spp., Gluconobacter oxydans, Klebsiella pneumoniae, etc. However, the role of PqqB is quite ambiguous as its functional role has been contradicted in many studies. In the present study, we selected Pseudomonas stutzeri - a well-known P solubilizing bacterium as a representative species of the Pseudomonas genus on the basis of phylogenetic and statistical analyses of PqqB proteins. A 3 D model was generated for this protein. Docking of PqqB with PQQ showed good interaction with a theoretical binding affinity of -7.4 kcal/mol. On the other hand, docking of PqqC with 3a-(2-amino-2-carboxy-ethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydro-quinoline-7,9-dicarboxylic acid (AHQQ, immediate precursor of PQQ) showed strong interaction (-10.4 kcal/mol) but the same was low with PQQ (-6.4 kcal/mol). Molecular dynamic simulation of both the complexes showed stable conformation. The binding energy of PqqB-PQQ complex (-182.710 ± 16.585 kJ/mol) was greater than PqqC-PQQ complex (-166.114 ± 12.027 kJ/mol). The results clearly indicated that kinetically there is a possibility that after cyclization of AHQQ to PQQ by PqqC, PQQ can be taken up by PqqB and transported to periplasm for the oxidation of glucose. To the best of our knowledge, this is the first attempt to understand the biological role of PqqB on the basis of molecular interactions and dynamics.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Prassan Choudhary
- Microbial Technology Unit-II, ICAR-National Bureau of Agriculturally Important Microorganisms, Mau Nath Bhanjan, India
| | - Arpan Bhowmik
- ICAR-Indian Agricultural Statistics Research Institute (IASRI), New Delhi, India
| | - Hillol Chakdar
- Microbial Technology Unit-II, ICAR-National Bureau of Agriculturally Important Microorganisms, Mau Nath Bhanjan, India
| | | | | | | | - Kumar Murugan
- Microbial Technology Unit-II, ICAR-National Bureau of Agriculturally Important Microorganisms, Mau Nath Bhanjan, India
| | - Sunil Kumar
- Centre for Agricultural Bioinformatics (CABIN), ICAR - Indian Agricultural Statistics Research Institute (IASRI), New Delhi, India
| | - Anil Kumar Saxena
- Microbial Technology Unit-II, ICAR-National Bureau of Agriculturally Important Microorganisms, Mau Nath Bhanjan, India
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Pandian SRK, Pavadai P, Vellaisamy S, Ravishankar V, Palanisamy P, Sundar LM, Chandramohan V, Sankaranarayanan M, Panneerselvam T, Kunjiappan S. Formulation and evaluation of rutin-loaded solid lipid nanoparticles for the treatment of brain tumor. Naunyn Schmiedebergs Arch Pharmacol 2020; 394:735-749. [PMID: 33156389 DOI: 10.1007/s00210-020-02015-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 10/29/2020] [Indexed: 12/14/2022]
Abstract
The primary requirement for curing cancer is the delivery of essential drug load at the cancer microenvironment with therapeutic efficacy. Considering this, the present study aims to formulate "Rutin"-encapsulated solid lipid nanoparticles (SLNs) for effective brain delivery across the blood-brain barrier (BBB). Rutin-loaded SLNs were fabricated by oil-in-water microemulsion technique and were characterized for their physicochemical properties. The in vivo biodistribution study of rutin-loaded SLNs was studied using Rattus norvegicus rats. Subsequently, in silico molecular docking and dynamic calculations were performed to examine the binding affinity as well as stability of rutin at the active site of target protein "epidermal growth factor receptor (EGFR)." Formulated rutin-loaded SLNs were predominantly spherical in shape with an average particle diameter of 100 nm. Additionally, the biocompatibility and stability have been proved in vitro. The presence and biodistribution of rutin in vivo after 54 h of injection were observed as 15.23 ± 0.32% in the brain, 8.68 ± 0.63% in the heart, 4.78 ± 0.28% in the kidney, 5.04 ± 0.37% in the liver, 0.92 ± 0.04% in the lung, and 11.52 ± 0.65% in the spleen, respectively. Molecular docking results revealed the higher binding energy of - 150.973 kJ/mol of rutin with EGFR. Molecular dynamic simulation studies demonstrated that rutin with EGFR receptor complex was highly stable at 30 ns. The observed results exemplified that the formulated rutin-loaded SLNs were stable in circulation for a period up to 5 days. Thus, rutin-encapsulated SLN formulations can be used as a promising vector to target tumors across BBB. Graphical abstract.
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Affiliation(s)
- Sureshbabu Ram Kumar Pandian
- Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu, 626126, India
| | - Parasuraman Pavadai
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, M S R Nagar, Bengaluru, Karnataka, 560054, India
| | - Sivakumar Vellaisamy
- Department of Pharmaceutics, Arulmigu Kalasalingam College of Pharmacy, Krishnankoil, Tamilnadu, 626126, India
| | - Vigneshwaran Ravishankar
- Department of Biotechnology, Mepco Schlenk Engineering College, Sivakasi, Tamilnadu, 626005, India
| | - Ponnusamy Palanisamy
- School of Mechanical Engineering, Vellore Institute of Technology, Vellore, Tamilnadu, 632014, India
| | - Lakshmi M Sundar
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, M S R Nagar, Bengaluru, Karnataka, 560054, India
| | - Vivek Chandramohan
- Department of Biotechnology, Siddaganga Institute of Technology, Tumakuru, Karnataka, 572103, India
| | | | - Theivendren Panneerselvam
- Department of Pharmaceutical Chemistry, Swamy Vivekananda College of Pharmacy, Elayampalayam, Namakkal, Tamilnadu, 637205, India.
| | - Selvaraj Kunjiappan
- Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu, 626126, India.
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Satapathy P, Prakash JK, Gowda VC, More SS, K M, Chandramohan V, Zameer F. Targeting Imd pathway receptor in Drosophila melanogaster and repurposing of phyto-inhibitors: structural modulation and molecular dynamics. J Biomol Struct Dyn 2020; 40:1659-1670. [PMID: 33050786 DOI: 10.1080/07391102.2020.1831611] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Dysbiosis is a major cause of disease in an individual, generally initiated in the gastrointestinal tract. The gut, also known as the second brain, constitutes a major role in immune signaling. To study the immunity cascade, the Drosophila model was considered targeting the Imd pathway receptor (2F2L) located in the midgut. This receptor further initiates the immune signaling mechanism influenced by bacteria. To inhibit the Imd pathway, the crystal structure of Imd with PDB: 2F2L was considered for the screening of suitable ligand/inhibitor. In light of our previous studies, repurposing of anti-diabetic ligands from the banana plant namely lupeol (LUP), stigmasterol (STI), β-sitosterol (BST) and umbelliferone (UMB) were screened. This study identifies the potential inhibitor along with the tracheal toxin (TCT), a major peptidoglycan constituent of microbes. The molecular docking and molecular dynamics simulation of complexes 2F2L-MLD, 2F2L- CAP, 2F2L-LUP, 2F2L-BST, 2F2L-STI and 2F2L-UMB elucidates the intermolecular interaction into the inhibitory property of ligands. The results of this study infer LUP and UMB as better ligands with high stability and functionality among the screened candidates. This study provides insights into the dysbiosis and its amelioration by plant-derived molecules. The identified drugs (LUP & UMB) will probably act as an inhibitor against microbial dysbiosis and other related pathogenesis (diabetes and diabetic neuropathy). Further, this study will widen avenues in fly biology research and which could be used as a therapeutic model in the rapid, reliable and reproducible screening of phytobiologics in complementary and alternative medicine for various lifestyle associated complications.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Pankaj Satapathy
- School of Basic and Applied Sciences, Department of Biological Sciences, Dayananda Sagar University, Bengaluru, Karnataka, India
| | - Jeevan Kallur Prakash
- Department of Biotechnology, Siddaganga Institute of Technology, Tumakuru, Karnataka, India
| | - V Chirag Gowda
- Department of Biotechnology, Siddaganga Institute of Technology, Tumakuru, Karnataka, India
| | - Sunil S More
- School of Basic and Applied Sciences, Department of Biological Sciences, Dayananda Sagar University, Bengaluru, Karnataka, India
| | - Muthuchelian K
- School of Basic and Applied Sciences, Department of Biological Sciences, Dayananda Sagar University, Bengaluru, Karnataka, India
| | - Vivek Chandramohan
- Department of Biotechnology, Siddaganga Institute of Technology, Tumakuru, Karnataka, India
| | - Farhan Zameer
- School of Basic and Applied Sciences, Department of Biological Sciences, Dayananda Sagar University, Bengaluru, Karnataka, India
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23
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Banerjee A, Czinn SJ, Reiter RJ, Blanchard TG. Crosstalk between endoplasmic reticulum stress and anti-viral activities: A novel therapeutic target for COVID-19. Life Sci 2020; 255:117842. [PMID: 32454157 PMCID: PMC7245231 DOI: 10.1016/j.lfs.2020.117842] [Citation(s) in RCA: 84] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Revised: 05/21/2020] [Accepted: 05/21/2020] [Indexed: 02/07/2023]
Abstract
The outbreak of COVID-19 caused by 2019–nCov/SARS-CoV-2 has become a pandemic with an urgent need for understanding the mechanisms and identifying a treatment. Viral infections including SARS-CoV are associated with increased levels of reactive oxygen species, disturbances of Ca++ caused by unfolded protein response (UPR) mediated by endoplasmic reticulum (ER) stress and is due to the exploitation of virus's own protein i.e., viroporins into the host cells. Several clinical trials are on-going including testing Remdesivir (anti-viral), Chloroquine and Hydroxychloroquine derivatives (anti-malarial drugs) etc. Unfortunately, each drug has specific limitations. Herein, we review the viral protein involvement to activate ER stress transducers (IRE-1, PERK, ATF-6) and their downstream signals; and evaluate combination therapies for COVID-19 mediated ER stress alterations. Melatonin is an immunoregulator, anti-pyretic, antioxidant, anti-inflammatory and ER stress modulator during viral infections. It enhances protective mechanisms for respiratory tract disorders. Andrographolide, isolated from Andrographis paniculata, has versatile biological activities including immunomodulation and determining SARS-CoV-2 binding site. Considering the properties of both compounds in terms of anti-inflammatory, antioxidant, anti-pyrogenic, anti-viral and ER stress modulation and computational approaches revealing andrographolide docks with the SARS-CoV2 binding site, we predict that this combination therapy may have potential utility against COVID-19.
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Affiliation(s)
- Aditi Banerjee
- Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
| | - Steven J Czinn
- Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Russel J Reiter
- Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, TX 78229, USA
| | - Thomas G Blanchard
- Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USA
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24
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Li F, Lee EM, Sun X, Wang D, Tang H, Zhou GC. Design, synthesis and discovery of andrographolide derivatives against Zika virus infection. Eur J Med Chem 2020; 187:111925. [PMID: 31838328 PMCID: PMC6980694 DOI: 10.1016/j.ejmech.2019.111925] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 11/27/2019] [Accepted: 11/28/2019] [Indexed: 12/14/2022]
Abstract
The Zika endemic established by imported and local transmission is of significant concern and effective anti-ZIKV drugs remain an urgent unmet need. As andrographolide was identified to be an inhibitor of DENV and CHIKV and the importance of quinoline structure against infectious diseases was considered, we are interested in studying its andrographolide derivatives with quinoline moiety against Zika virus infection. In addition to screening eight in-house derivatives of andrographolide, sixteen new derivatives were designed, synthesized and tested against Zika virus infection. Among these compounds, two most potent anti-Zika compounds of 19-acetylated 14α-(5',7'-dichloro-8'-quinolyloxy) derivative 17b and 14β-(8'-quinolyloxy)-3,19- diol derivative 3 with the highest selectivity were discovered. The SAR analysis indicates that rational and optimal combined modification/s at 3-, 14-, or 19-positions can make derivatives less toxic and more potent against Zika infection, and both of 3 and 17b are suitable as leads for designing new generation of andrographolide derivatives with quinoline or its structure- and property-related moieties against Zika virus and other arboviruses.
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Affiliation(s)
- Feng Li
- School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, Jiangsu, 211800, China
| | - Emily M Lee
- Department of Biological Science, Florida State University, Tallahassee, FL, 32306, USA
| | - Xia Sun
- School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, Jiangsu, 211800, China
| | - Decai Wang
- School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, Jiangsu, 211800, China
| | - Hengli Tang
- Department of Biological Science, Florida State University, Tallahassee, FL, 32306, USA.
| | - Guo-Chun Zhou
- School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, Jiangsu, 211800, China.
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25
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Uma K, Lalithamba HS, Chandramohan V, Lingaraju K. A Facile Synthesis of Hydroxamic Acids ofNα-Protected Amino Acids Employing BDMS, a Study of Their Molecular Docking and Their Antibacterial Activities. ORG PREP PROCED INT 2019. [DOI: 10.1080/00304948.2019.1579039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Affiliation(s)
- K. Uma
- Department of Chemistry, Siddaganga Institute of Technology, B.H. Road, Tumakuru-572 103, Karnataka, India
| | - H. S. Lalithamba
- Department of Chemistry, Siddaganga Institute of Technology, B.H. Road, Tumakuru-572 103, Karnataka, India
| | - V. Chandramohan
- Department of Biotechnology, Siddaganga Institute of Technology, B.H. Road, Tumakuru-572 103, Karnataka, India
| | - K. Lingaraju
- Department of Biotechnology, Tumkur University, B.H. Road, Tumakuru-572 103, Karnataka, India
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26
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Li H, Huang MH, Jiang JD, Peng ZG. Hepatitis C: From inflammatory pathogenesis to anti-inflammatory/hepatoprotective therapy. World J Gastroenterol 2018; 24:5297-5311. [PMID: 30598575 PMCID: PMC6305530 DOI: 10.3748/wjg.v24.i47.5297] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 11/27/2018] [Accepted: 12/01/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection commonly causes progressive liver diseases that deteriorate from chronic inflammation to fibrosis, cirrhosis and even to hepatocellular carcinoma. A long-term, persistent and uncontrolled inflammatory response is a hallmark of these diseases and further leads to hepatic injury and more severe disease progression. The levels of inflammatory cytokines and chemokines change with the states of infection and treatment, and therefore, they may serve as candidate biomarkers for disease progression and therapeutic effects. The mechanisms of HCV-induced inflammation involve classic pathogen pattern recognition, inflammasome activation, intrahepatic inflammatory cascade response, and oxidative and endoplasmic reticulum stress. Direct-acting antivirals (DAAs) are the first-choice therapy for effectively eliminating HCV, but DAAs alone are not sufficient to block the uncontrolled inflammation and severe liver injury in HCV-infected individuals. Some patients who achieve a sustained virologic response after DAA therapy are still at a long-term risk for progression to liver cirrhosis and hepatocellular carcinoma. Therefore, coupling with anti-inflammatory/hepatoprotective agents with anti-HCV effects is a promising therapeutic regimen for these patients during or after treatment with DAAs. In this review, we discuss the relationship between inflammatory mediators and HCV infection, summarize the mechanisms of HCV-induced inflammation, and describe the potential roles of anti-inflammatory/hepatoprotective drugs with anti-HCV activity in the treatment of advanced HCV infection.
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Affiliation(s)
- Hu Li
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Meng-Hao Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, United States
| | - Jian-Dong Jiang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Zong-Gen Peng
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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Quintero-Gil C, Parra-Suescún J, Lopez-Herrera A, Orduz S. In-silico design and molecular docking evaluation of peptides derivatives from bacteriocins and porcine beta defensin-2 as inhibitors of Hepatitis E virus capsid protein. Virusdisease 2017; 28:281-288. [PMID: 29291214 DOI: 10.1007/s13337-017-0383-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Accepted: 05/29/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) is considered the main etiological agent that causes acute hepatitis. It is estimated that 20 million cases occur annually worldwide, reaching mortality rates of 28% in pregnant women. To date, available treatments and vaccines have not been entirely effective. In this study, six antiviral peptides derived from the sequences of porcine Beta-Defensin-2 and bacteriocins Nisin and Subtilosin were generate using in silico tools in order to propose new antiviral agents. Through the use of molecular docking, interactions between the HEV capsid protein and the six new antiviral peptide candidates were evaluated. A peptide of 15 residues derived from Subtilosin showed the best docking energy (-7.0 kcal/mol) with the capsid protein. This is the first report to our knowledge involving a non-well study viral protein interacting with peptides susceptibles to being synthesized, and that could be subsequently evaluated in vitro; moreover, this study provide novel information on the nature of the dimerization pocket of the HEV capsid protein, and could help to understand the first steps in the viral replication cycle, needed for the virus entry to the host cell.
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Affiliation(s)
- Carolina Quintero-Gil
- Escuela de Biociencias, Grupo Biología Funcional, Universidad Nacional de Colombia, Sede Medellín, Calle 59A # 63-20, Medellín, Colombia
| | - Jaime Parra-Suescún
- Facultad de Ciencias Agrarias, Grupo Biodiversidad y Genética Molecular (BIOGEM), Universidad Nacional de Colombia, Sede Medellín, Calle 59A # 63-20, Medellín, Colombia
| | - Albeiro Lopez-Herrera
- Facultad de Ciencias Agrarias, Grupo Biodiversidad y Genética Molecular (BIOGEM), Universidad Nacional de Colombia, Sede Medellín, Calle 59A # 63-20, Medellín, Colombia
| | - Sergio Orduz
- Escuela de Biociencias, Grupo Biología Funcional, Universidad Nacional de Colombia, Sede Medellín, Calle 59A # 63-20, Medellín, Colombia
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28
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Broad-spectrum antiviral properties of andrographolide. Arch Virol 2016; 162:611-623. [PMID: 27896563 DOI: 10.1007/s00705-016-3166-3] [Citation(s) in RCA: 111] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Accepted: 10/20/2016] [Indexed: 01/01/2023]
Abstract
Andrographolide, a diterpenoid, is known for its anti-inflammatory effects. It can be isolated from various plants of the genus Andrographis, commonly known as 'creat'. This purified compound has been tested for its anti-inflammatory effects in various stressful conditions, such as ischemia, pyrogenesis, arthritis, hepatic or neural toxicity, carcinoma, and oxidative stress, Apart from its anti-inflammatory effects, andrographolide also exhibits immunomodulatory effects by effectively enhancing cytotoxic T cells, natural killer (NK) cells, phagocytosis, and antibody-dependent cell-mediated cytotoxicity (ADCC). All these properties of andrographolide form the foundation for the use of this miraculous compound to restrain virus replication and virus-induced pathogenesis. The present article covers antiviral properties of andrographolide in variety of viral infections, with the hope of developing of a new highly potent antiviral drug with multiple effects.
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29
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Yoganarasimha B, Chandramohan V, Krishna Murthy TP, Gangadharappa BS, Siddaiah GB, Hanumanthappa M. Prediction of deleterious single nucleotide polymorphisms and their effect on the sequence and structure of the human CCND1 gene. J Taibah Univ Med Sci 2016; 12:221-228. [PMID: 31435243 PMCID: PMC6695066 DOI: 10.1016/j.jtumed.2016.07.009] [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: 06/17/2016] [Revised: 07/25/2016] [Accepted: 07/31/2016] [Indexed: 11/24/2022] Open
Abstract
Objective The CCND1 gene expresses a protein, G1/S-specific cyclin, that regulates the G1/S transition in the cell cycle and also inhibits retinoblastoma (RB) proteins. Overexpression or rearrangements of this gene can result in various tumours. This study aimed to identify possible deleterious non-synonymous single nucleotide polymorphisms (SNP's) of CCND1 using computational methods. Methods SNPs in the human CCND1 gene were retrieved from dbSNP. These SNPs were screened by the Sorting Intolerant From Tolerant (SIFT) algorithm and the PredictSNP classification. Mutants with deleterious SNPs were built using Discovery Studio 3.5, and dynamics studies were performed on native and mutant varieties. Results In Homo sapiens, 1194 SNPs were found, of which 94 were missense and 2 were nonsense SNPs. Three SNPs were found to be deleterious. Molecular dynamics and trajectory analysis showed that there was a significant deviation of the root mean square deviation (RMSD) values in the N216K mutant from the values of the native protein. Conclusion Based on this study, we propose that the SNP with SNP ID rs112525097 (NM_053056.2:c.648C>G) might cause aberrations in CCND1, which might lead to a change in the function of the G1/S-specific cyclin protein. This, in turn, may lead to the development of acute myeloid leukaemia (AML).
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Affiliation(s)
- Bharath Yoganarasimha
- Department of Biotechnology, M. S. Ramaiah Institute of Technology, Bengaluru, Karnataka, India
| | - Vivek Chandramohan
- Department of Biotechnology, Siddaganga Institute of Technology, Tumakuru, Karnataka, India
| | | | - Bhavya S Gangadharappa
- Department of Biotechnology, M. S. Ramaiah Institute of Technology, Bengaluru, Karnataka, India
| | | | - Makari Hanumanthappa
- Department of Biotechnology, IDSG Government College, Chikkamagaluru, Karnataka, India
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