Virtual Screening of Natural Compounds to Identify Potential Inhibitors of COVID-19 Protease using Molecular Docking

Abstract

COVID-19 disease has spread quickly across the globe after its first detection in late December 2019 in Wuhan, China. The disease is considered as a potential global health threat by world health organization due to its high emerging deaths. Coronaviruses are transmitted by respiratory aerosols producing mild upper respiratory infections. Currently, no vaccine or specific COVID-19 inhibitors are available for treatment except repurposed drugs. The COVID-19 virus genome has ~30,000 nucleotides. Its replicase gene encodes overlapping polyproteins necessary for viral replication and transcription. Recently COVID-19 main protease was successfully crystallized and made available in Protein Data Bank for public use. Several studies report medicinal plants to have antiviral bioactivities. Application of in silico computer‐based docking studies involving small molecules could be time saving for irrelevant in vivo models. In the present study, we have investigated 500 natural compounds from different plants having antiviral properties. We have also screened several protease inhibitors and other repurposed drugs claimed to be active against COVID-19. The docking was performed on Autodock vina, using grid size 22, 22, 24 along the X, Y, and Z axes with 1.000 A˚ spacing. The docked positions in binding pockets were visualized using Discovery studio 3.5 software. Most of the repurposed protease inhibitors were having good binding energy, saquinavir being the most potent. Among natural compounds, jervine and isoacteoside were found to be having good binding with protease protein. It was observed that flavonoid was the commonest chemical group amongst most potent natural compounds. The amino acids Thr26, Asn142, Gly143, Ser144, Cys145, His163, and Glu166 showed strong H-bond interactions with docked compounds. The conclusion of the recent study will help researchers to identify the better drug to battle COVID-19. To be brief, our findings emphasize a promising pharmaceutical perspective for targeting main protease of novel coronavirus. However further preclinical and clinical trials should be carried out to validate these potential compounds.