Yee Siew Choong*, Theam Soon Lim, Hanyun Liu, Rubin Jiang, Zimu Cai and Yuan Ge* Pages 429 - 435 ( 7 )
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 rely on its RNA-dependent RNA polymerase (RdRP), which is a therapeutic target of clinical importance. Crystal structure of SARS-CoV-2 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 anti-viral effects.
Methods: 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: 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 COVID-19 treatment in the near future.
SARS-CoV-2, COVID-19, RNA-dependent RNA polymerase, docking simulation, binding sites, allosteric nonnucleoside inhibitors.
Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang, Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang, Department of Infectious Diseases, Affiliated Hospital of Qingdao University, Qingdao, College of Marine Life Science, Ocean University of China, Qingdao, College of Marine Life Science, Ocean University of China, Qingdao, College of Marine Life Science, Ocean University of China, Qingdao