New Strategy for COVID-19: An Evolutionary Role for RGD Motif in SARS-CoV-2 and Potential Inhibitors for Virus Infection.
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ABSTRACT:
SUBMITTER: Yan S
PROVIDER: S-EPMC7303337 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
New Strategy for COVID-19: An Evolutionary Role for RGD Motif in SARS-CoV-2 and Potential Inhibitors for Virus Infection.
Yan Shijia S Sun Haixia H Bu Xianzhang X Wan Guohui G
Frontiers in pharmacology 20200612
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Project description:SARS-CoV-2 infection results in impaired interferon response in severe COVID-19 patients. However, how SARS-CoV-2 interferes with host immune response is incompletely understood. Here, we sequenced small RNAs from SARS-CoV-2-infected human cells and identified a microRNA (miRNA) derived from a recently evolved region of the viral genome. We show that the virus-derived miRNA produces two miRNA isoforms in infected cells by the enzyme Dicer and they are loaded into Argonaute proteins. Moreover, the predominant miRNA isoform targets the 3´UTR of interferon-stimulated genes and represses their expression in a miRNA-like fashion. Finally, the two viral miRNA isoforms were detected in nasopharyngeal swabs from COVID-19 patients. We propose that SARS-CoV-2 can potentially employ a virus-derived miRNA to hijack the host miRNA machinery which can lead to evasion of the interferon-mediated immune response.
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Project description:BackgroundThe present pandemic situation due to coronavirus has led to the search for newer prevention, diagnostic, and treatment methods. The onset of the corona infection in a human results in acute respiratory illness followed by death if not diagnosed and treated with suitable antiretroviral drugs. With the unavailability of the targeted drug treatment, several repurposed drugs are being used for treatment. However, the side-effects of the drugs urges us to move to a search for newer synthetic- or phytochemical-based drugs. The present study investigates the use of various phytochemicals virtually screened from various plant sources in Western Ghats, India, and subsequently molecular docking studies were performed to identify the efficacy of the drug in retroviral infection particularly coronavirus infection.ResultsOut of 57 phytochemicals screened initially based on the structural and physicochemical properties, 39 were effectively used for the docking analysis. Finally, 5 lead compounds with highest hydrophobic interaction and number of H-bonds were screened. Results from the interaction analysis suggest Piperolactam A to be pocketed well with good hydrophobic interaction with the residues in the binding region R1. ADME and toxicity profiling also reveals Piperolactam A with higher LogS values indicating higher permeation and hydrophilicity. Toxicity profiling suggests that the 5 screened compounds to be relatively safe.ConclusionThe in silico methods used in this study suggests that the compound Piperolactam A to be the most effective inhibitor of S-protein from binding to the GRP78 receptor. By blocking the binding of the S-protein to the CS-GRP78 cell surface receptor, they can inhibit the binding of the virus to the host.Supplementary informationThe online version contains supplementary material available at 10.1186/s43088-021-00095-x.
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