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Reyes CDG, Onigbinde S, Sanni A, Bennett AI, Jiang P, Daramola O, Ahmadi P, Fowowe M, Atashi M, Sandilya V, Hakim MA, Mechref Y. N-Glycome Profile of the Spike Protein S1: Systemic and Comparative Analysis from Eleven Variants of SARS-CoV-2. Biomolecules 2023; 13:1421. [PMID: 37759821 PMCID: PMC10526240 DOI: 10.3390/biom13091421] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Revised: 09/01/2023] [Accepted: 09/08/2023] [Indexed: 09/29/2023] Open
Abstract
The SARS-CoV-2 virus rapidly spread worldwide, threatening public health. Since it emerged, the scientific community has been engaged in the development of effective therapeutics and vaccines. The subunit S1 in the spike protein of SARS-CoV-2 mediates the viral entry into the host and is therefore one of the major research targets. The S1 protein is extensively glycosylated, and there is compelling evidence that glycans protect the virus' active site from the human defense system. Therefore, investigation of the S1 protein glycome alterations in the different virus variants will provide a view of the glycan evolution and its relationship with the virus pathogenesis. In this study, we explored the N-glycosylation expression of the S1 protein for eleven SARS-CoV-2 variants: five variants of concern (VOC), including alpha, beta, gamma, delta, and omicron, and six variants of interest (VOI), including epsilon, eta, iota, lambda, kappa, and mu. The results showed significant differences in the N-glycome abundance of all variants. The N-glycome of the VOC showed a large increase in the abundance of sialofucosylated glycans, with the greatest abundance in the omicron variant. In contrast, the results showed a large abundance of fucosylated glycans for most of the VOI. Two glycan compositions, GlcNAc4,Hex5,Fuc,NeuAc (4-5-1-1) and GlcNAc6,Hex8,Fuc,NeuAc (6-8-1-1), were the most abundant structures across all variants. We believe that our data will contribute to understanding the S1 protein's structural differences between SARS-CoV-2 mutations.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Yehia Mechref
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USA; (C.D.G.R.); (S.O.); (A.S.); (A.I.B.); (P.J.); (O.D.); (P.A.); (M.F.); (M.A.); (V.S.); (M.A.H.)
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2
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Das K, Paul S, Mukherjee T, Ghosh A, Sharma A, Shankar P, Gupta S, Keshava S, Parashar D. Beyond Macromolecules: Extracellular Vesicles as Regulators of Inflammatory Diseases. Cells 2023; 12:1963. [PMID: 37566042 PMCID: PMC10417494 DOI: 10.3390/cells12151963] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 07/26/2023] [Accepted: 07/27/2023] [Indexed: 08/12/2023] Open
Abstract
Inflammation is the defense mechanism of the immune system against harmful stimuli such as pathogens, toxic compounds, damaged cells, radiation, etc., and is characterized by tissue redness, swelling, heat generation, pain, and loss of tissue functions. Inflammation is essential in the recruitment of immune cells at the site of infection, which not only aids in the elimination of the cause, but also initiates the healing process. However, prolonged inflammation often brings about several chronic inflammatory disorders; hence, a balance between the pro- and anti-inflammatory responses is essential in order to eliminate the cause while producing the least damage to the host. A growing body of evidence indicates that extracellular vesicles (EVs) play a major role in cell-cell communication via the transfer of bioactive molecules in the form of proteins, lipids, DNA, RNAs, miRNAs, etc., between the cells. The present review provides a brief classification of the EVs followed by a detailed description of how EVs contribute to the pathogenesis of various inflammation-associated diseases and their implications as a therapeutic measure. The latter part of the review also highlights how EVs act as a bridging entity in blood coagulation disorders and associated inflammation. The findings illustrated in the present review may open a new therapeutic window to target EV-associated inflammatory responses, thereby minimizing the negative outcomes.
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Affiliation(s)
- Kaushik Das
- Department of Cellular and Molecular Biology, The University of Texas at Tyler Health Science Center, Tyler, TX 75708, USA
| | - Subhojit Paul
- School of Biological Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India; (S.P.); (A.G.)
| | - Tanmoy Mukherjee
- School of Medicine, The University of Texas at Tyler Health Science Center, Tyler, TX 75708, USA;
| | - Arnab Ghosh
- School of Biological Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India; (S.P.); (A.G.)
| | - Anshul Sharma
- Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA;
| | - Prem Shankar
- Department of Neurobiology, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA;
| | - Saurabh Gupta
- Department of Biotechnology, GLA University, Mathura 281406, India;
| | - Shiva Keshava
- Department of Cellular and Molecular Biology, The University of Texas at Tyler Health Science Center, Tyler, TX 75708, USA
| | - Deepak Parashar
- Department of Medicine, Division of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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A Long-Running Arms Race between APOBEC1 Genes and Retroviruses in Tetrapods. J Virol 2023; 97:e0179522. [PMID: 36598198 PMCID: PMC9888297 DOI: 10.1128/jvi.01795-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Activation-induced cytidine deaminase/apolipoprotein B mRNA editing catalytic polypeptide-like (AID/APOBEC) proteins are cytosine deaminases implicated in diverse biological functions. APOBEC1 (A1) proteins have long been thought to regulate lipid metabolism, whereas the evolutionary significance of A1 proteins in antiviral defense remains largely obscure. Endogenous retroviruses (ERVs) document past retroviral infections and are ubiquitous within the vertebrate genomes. Here, we identify the A1 gene repertoire, characterize the A1-mediated mutation footprints in ERVs, and interrogate the evolutionary arms race between A1 genes and ERVs across vertebrate species. We find that A1 genes are widely present in tetrapods, recurrently amplified and lost in certain lineages, suggesting that A1 genes might have originated during the early evolution of tetrapods. A1-mediated mutation footprints can be detected in ERVs across tetrapods. Moreover, A1 genes appear to have experienced episodic positive selection in many tetrapod lineages. Taken together, we propose that a long-running arms race between A1 genes and retroviruses might have persisted throughout the evolutionary course of tetrapods. IMPORTANCE APOBEC3 (A3) genes have been thought to function in defense against retroviruses, whereas the evolutionary significance of A1 proteins in antiviral defense remains largely obscure. In this study, we identify the A1 gene repertoire, characterize the A1-mediated mutation footprints in endogenous retroviruses (ERVs), and explore the evolutionary arms race between A1 genes and ERVs across vertebrate species. We found A1 proteins originated during the early evolution of tetrapods, and detected the footprints of A1-induced hypermutations in retroviral fossils. A1 genes appear to have experienced pervasive positive selection in tetrapods. Our study indicates a long-running arms race between A1 genes and retroviruses taking place throughout the evolutionary course of tetrapods.
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Reno U, Regaldo L, Ojeda G, Schmuck J, Romero N, Polla W, Kergaravat SV, Gagneten AM. Wastewater-Based Epidemiology: Detection of SARS-CoV-2 RNA in Different Stages of Domestic Wastewater Treatment in Santa Fe, Argentina. WATER, AIR, AND SOIL POLLUTION 2022; 233:372. [PMID: 36090741 PMCID: PMC9440651 DOI: 10.1007/s11270-022-05772-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 07/10/2022] [Indexed: 06/15/2023]
Abstract
The COVID-19 pandemic affected human life at every level. In this study, we analyzed genetic markers (N and ORF1ab, RNA genes) of SARS-CoV-2 in domestic wastewaters (DWW) in San Justo City (Santa Fe, Argentina), using reverse transcription-quantitative real-time PCR. Out of the 30 analyzed samples, 30% were positive for SARS-CoV-2 RNA. Of the total positive samples, 77% correspond to untreated DWW, 23% to pre-chlorination, and no SARS-CoV-2 RNA was registered at the post-chlorination sampling site. The viral loads of N and OFR1ab genes decreased significantly along the treatment process, and the increase in the number of viral copies of the N gene could anticipate, by 6 days, the number of clinical cases in the population. The concentration of chlorine recommended by the WHO (≥ 0.5 mg L-1 after at least 30 min of contact time at pH 8.0) successfully removed SARS-CoV-2 RNA from DWW. The efficiency of wastewater-based epidemiology (WBE) confirms the need to control and increase DWW treatment systems on a regional and global scale. This work could contribute to building a network for WBE to monitor SARS-CoV-2 in wastewaters during the pandemic waves and the epidemic remission phase. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11270-022-05772-w.
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Affiliation(s)
- Ulises Reno
- Ecotoxicology Laboratory, Department of Natural Sciences, Faculty of Humanities and Sciences, National University of Littoral (UNL), 3000 Santa Fe, Argentina
- National Council for Scientific and Technological Research (CONICET), 3000 Santa Fe, Argentina
| | - Luciana Regaldo
- Ecotoxicology Laboratory, Department of Natural Sciences, Faculty of Humanities and Sciences, National University of Littoral (UNL), 3000 Santa Fe, Argentina
- National Council for Scientific and Technological Research (CONICET), 3000 Santa Fe, Argentina
| | - Guillermo Ojeda
- Central Laboratory, Ministry of Health, 3000 Santa Fe, Argentina
| | - Josefina Schmuck
- Ecotoxicology Laboratory, Department of Natural Sciences, Faculty of Humanities and Sciences, National University of Littoral (UNL), 3000 Santa Fe, Argentina
- National Council for Scientific and Technological Research (CONICET), 3000 Santa Fe, Argentina
| | - Natalí Romero
- Ecotoxicology Laboratory, Department of Natural Sciences, Faculty of Humanities and Sciences, National University of Littoral (UNL), 3000 Santa Fe, Argentina
- National Council for Scientific and Technological Research (CONICET), 3000 Santa Fe, Argentina
| | - Wanda Polla
- Ecotoxicology Laboratory, Department of Natural Sciences, Faculty of Humanities and Sciences, National University of Littoral (UNL), 3000 Santa Fe, Argentina
| | - Silvina V. Kergaravat
- Ecotoxicology Laboratory, Department of Natural Sciences, Faculty of Humanities and Sciences, National University of Littoral (UNL), 3000 Santa Fe, Argentina
- National Council for Scientific and Technological Research (CONICET), 3000 Santa Fe, Argentina
| | - Ana María Gagneten
- Ecotoxicology Laboratory, Department of Natural Sciences, Faculty of Humanities and Sciences, National University of Littoral (UNL), 3000 Santa Fe, Argentina
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Ebubeogu AF, Ozigbu CE, Maswadi K, Seixas A, Ofem P, Conserve DF. Predicting the number of COVID-19 infections and deaths in USA. Global Health 2022; 18:37. [PMID: 35346262 PMCID: PMC8959784 DOI: 10.1186/s12992-022-00827-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 03/03/2022] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Uncertainties surrounding the 2019 novel coronavirus (COVID-19) remain a major global health challenge and requires attention. Researchers and medical experts have made remarkable efforts to reduce the number of cases and prevent future outbreaks through vaccines and other measures. However, there is little evidence on how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection entropy can be applied in predicting the possible number of infections and deaths. In addition, more studies on how the COVID-19 infection density contributes to the rise in infections are needed. This study demonstrates how the SARS-COV-2 daily infection entropy can be applied in predicting the number of infections within a given period. In addition, the infection density within a given population attributes to an increase in the number of COVID-19 cases and, consequently, the new variants. RESULTS Using the COVID-19 initial data reported by Johns Hopkins University, World Health Organization (WHO) and Global Initiative on Sharing All Influenza Data (GISAID), the result shows that the original SAR-COV-2 strain has R0<1 with an initial infection growth rate entropy of 9.11 bits for the United States (U.S.). At close proximity, the average infection time for an infected individual to infect others within a susceptible population is approximately 7 minutes. Assuming no vaccines were available, in the U.S., the number of infections could range between 41,220,199 and 82,440,398 in late March 2022 with approximately, 1,211,036 deaths. However, with the available vaccines, nearly 48 Million COVID-19 cases and 706, 437 deaths have been prevented. CONCLUSION The proposed technique will contribute to the ongoing investigation of the COVID-19 pandemic and a blueprint to address the uncertainties surrounding the pandemic.
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Affiliation(s)
| | - Chamberline Ekene Ozigbu
- Department of Health Services Policy and Management, Arnold School of Public, Health, Columbia, 29208, SC, United States
| | - Kholoud Maswadi
- Department of Management Information Systems, Jazan University, Jazan, 45142, Saudi Arabia
| | - Azizi Seixas
- Department of Psychiatry and Behavioral Sciences, The University of Miami Miller School of Medicine, Miami, 33136, FL, United States
| | - Paulinus Ofem
- Department of Software Engineering, University of Malaya, Kuala Lumpur, 50603, Malaysia
| | - Donaldson F Conserve
- Department of Prevention and Community Health, Milken Institute School of Public Health, The George Washington University, Washington, 20052, United States
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Akbar A, Malekian F, Baghban N, Kodam SP, Ullah M. Methodologies to Isolate and Purify Clinical Grade Extracellular Vesicles for Medical Applications. Cells 2022; 11:186. [PMID: 35053301 PMCID: PMC8774122 DOI: 10.3390/cells11020186] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 01/03/2022] [Accepted: 01/04/2022] [Indexed: 02/06/2023] Open
Abstract
The use of extracellular vesicles (EV) in nano drug delivery has been demonstrated in many previous studies. In this study, we discuss the sources of extracellular vesicles, including plant, salivary and urinary sources which are easily available but less sought after compared with blood and tissue. Extensive research in the past decade has established that the breadth of EV applications is wide. However, the efforts on standardizing the isolation and purification methods have not brought us to a point that can match the potential of extracellular vesicles for clinical use. The standardization can open doors for many researchers and clinicians alike to experiment with the proposed clinical uses with lesser concerns regarding untraceable side effects. It can make it easier to identify the mechanism of therapeutic benefits and to track the mechanism of any unforeseen effects observed.
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Affiliation(s)
- Asma Akbar
- Institute for Immunity and Transplantation, Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Palo Alto, CA 94304, USA; (A.A.); (F.M.); (N.B.); (S.P.K.)
| | - Farzaneh Malekian
- Institute for Immunity and Transplantation, Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Palo Alto, CA 94304, USA; (A.A.); (F.M.); (N.B.); (S.P.K.)
| | - Neda Baghban
- Institute for Immunity and Transplantation, Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Palo Alto, CA 94304, USA; (A.A.); (F.M.); (N.B.); (S.P.K.)
| | - Sai Priyanka Kodam
- Institute for Immunity and Transplantation, Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Palo Alto, CA 94304, USA; (A.A.); (F.M.); (N.B.); (S.P.K.)
| | - Mujib Ullah
- Institute for Immunity and Transplantation, Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Palo Alto, CA 94304, USA; (A.A.); (F.M.); (N.B.); (S.P.K.)
- Department of Cancer Immunology, Genentech Inc., South San Francisco, CA 94080, USA
- Molecular Medicine Department of Medicine, Stanford University, Palo Alto, CA 94304, USA
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