In silico analysis of RNA-dependent RNA polymerase of the SARS-CoV-2 and potentiality of the pre-existing drugs

Abstract

Background: The alarming increase in the number of SARS-CoV-2 cases worldwide, urgently demands far-reaching effective strategies to win the battle against emerging as well as re-emerging diseases. Many research laboratories are conducting clinical trials with different drugs, among which some became quite interestingly effective against this pandemic. Our aim is to investigate the potentiality of the pre-existing drugs and get a clear understanding of their effects on RNA-dependent RNA polymerase (RdRp) of the SARS-CoV-2. Methods: Multiple sequence alignment (MSA) alogwith molecular phylogeny analysis were performed using homologous sequences to identify the mutations within RdRp and evolutionary relationship. Based on the published literatures, we have chosen eight drug molecules like Ribavirin, Tenofovir, Sofosbuvir, IDX-184, YAK, Setrobuvir, Remdesivir and Galidesivir. Series of molecular docking studies between template RNA and RdRp of SARS-CoV-2 has been performed in absence or presence of those drugs and cofactors nsp7 and nsp8.Results: From MSA 13 exclusive mutations identified within RdRp of SARS-CoV-2 and phylogeny reveals its close relation with Bat coronavirus RaTG13. The interaction affinities and interacting residues as obtained from systematic molecular docking study led to a conclusion that the chosen drugs can prove to be effective against this pandemic partially. Conclusion: Therefore, designing of inhibitors which will specifically act against nsp12 and lower the binding affinity of nsp12 towards RNA template is necessary. In this article we additionally focus on the nsp7-8 hexadecameric complex and had suggested a list of amino acid residues of nsp12 and nsp7-8 complex to develop far-reaching effective drugs.