Theoretical and Computational Chemistry

Identification of Potential SARS-CoV-2 Inhibitors Using Flexible Docking Based Drug Repurposing of Antivirals



A selection of antiviral compounds from the Drug Repurposing Hub were screened as potential inhibitors against SARS-CoV-2 protein targets using CIFDock, a flexible docking method. CIFDock allows for a fully flexible active site of the protein-ligand complex and retaining of explicit water molecules throughout docking simulations. This method provides a more thorough conformational space search than is attainable by rigid docking methods, and thus a more accurate representation of the binding interactions between these antiviral compounds and the SARS-CoV-2 protein targets. Four proteins critical to viral function were selected as targets of the study: the main protease (Mpro), the papain-like protease (PLpro), the transmembrane protease (TMPRSS2), and the RNA-dependent RNA-polymerase (RdRp). The results reveal potential SARS-CoV-2 viral inhibitors from this library of antivirals, based on favorable Glide scores of the docked protein-ligand poses. The antiviral compounds brecanavir, mozenavir, palinavir, sovaprevir, and telinavir yielded excellent binding scores across all protease targets. Additionally, these particular antivirals have not yet been investigated in clinical trials nor in vitro studies regarding COVID-19. Therefore, these compounds can be recommended for further research against SARS-CoV-2, based on extensive docking analysis with relevant protein targets.


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Supplementary material

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Binding Residue Information and Antiviral Structures
Table S1 lists the residues selected to define the binding site of each of the target receptor proteins for docking. Figure S1 shows the structures of the protease inhibitors used in this docking study. Figure S2 shows the structures of the polymerase inhibitors used in this docking study.