Potential Inhibition of COVID-19 RNA-dependent RNA Polymerase by Hepatitis C Virus Non-nucleoside Inhibitors: An In-silico Perspective

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Author(s): Yee Siew Choong, Theam Soon Lim, Hanyun Liu, Rubin Jiang, Zimu Cai, Yuan Ge*

Journal Name: Letters in Drug Design & Discovery

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Abstract:

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel member of the genus betacoronavirus in the Coronaviridae family. It has been identified as the causative agent of coronavirus disease 2019 (COVID-19) spreading rapidly in Asia, America and Europe. Like some other RNA viruses, RNA replication and transcription of SARS-CoV-2 relies on its RNA-dependent RNA polymerase (RdRP), which is a therapeutic target of clinical importance. Crystal structure of SARS-CoV-2 that was solved recently (PDB ID 6M71) with some missing residues.

Objective: We used SARS-CoV-2 RdRP as a target protein to screen for possible chemical molecules with potential antiviral effects.

Method: Here we modelled the missing residues 896-905 via homology modelling and then analysed the interactions of Hepatitis C virus allosteric non-nucleoside inhibitors (NNIs) in the reported NNIs binding sites in SARS-CoV-2 RdRP.

Results and Discussion: We found that MK-3281, filibuvir, setrobuvir and dasabuvir might be able to inhibit SARS-CoV-2 RdRP based on their binding affinities in the respective binding sites.

Conclusion: Further in vitro and in vivo experimental research will be carried out to evaluate their effectiveness in COVID19 treatment in the near future.

Keywords: SARS-CoV-2, COVID-19, RNA-dependent RNA polymerase, docking simulation, binding sites, allosteric nonnucleoside inhibitors

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(E-pub Ahead of Print)
DOI: 10.2174/1570180817999201104123750
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