Structure based drug discovery by virtual screening of 3699 compounds against the crystal structures of six key SARS-CoV-2 proteins

Abstract BackgroundThe current Novel Coronavirus (SARS-CoV-2) pandemic is the third major outbreak of the 21st century which emerged in December 2019 from Wuhan, China. At present there are no known treatments or vaccines to cure or prevent the illness.ObjectiveThe objective of this study was to explore a list of potential drugs (herbal and antivirals) for their role in inhibiting activity and or replication of SARS-CoV-2 by using molecular docking onto the crystal structures of key viral proteins.MethodologyIn this study, we used molecular docking to estimate the binding affinities of 3699 drugs on the potential active sites of the 6 main SARS-CoV-2 proteins (Papain like protease, Main protease, ADP Ribose phosphatase, Spike protein, NSP-9 and NSP-10 to 16 complex). While other studies have mostly been performed on the homology models, we obtained the most recently submitted crystal structures of all 6 proteins from the protein data bank for this analysis.ResultsOur results showed the top ligands as Theasinensin A, Epigallocatechin, Theaflavin, Theasinensin A, Epigallocatechin and Favipiravir showing the highest binding affinities against papain-like protease, ADP ribose phosphatase, main protease, spike protein, RNA replicase (NSP-9) and methyl-transferase (NSP-16) respectively.ConclusionWe show that the compounds from our list with the greatest inhibitory potential against SARS-CoV-2 activity or replication include Theasinensin A, Epigallocatechin-3-gallate, Theaflavin, Favipiravir, Curucumin, Quercetin, Mitoxantrone, Amentoflavone, Colistin, Cimicifugic acid, Theaflavin, Silymarin and Chebulagic. We recommend further wet-lab and clinical testing of these compounds to further explore their role against SARS-CoV-2.