In-silico ADME and Docking-based Virtual Screening Study Aiming at the Sigma-Covalent Inhibition of SARS-CoV-2 RdRp

Abstract

The objectives of the study were to examine the virtual screening of the compounds and sigma-covalent inhibition of SARS-CoV-2 RdRp (RNA-Dependent RNA-Polymerase), which is conserved and is an essential enzyme for RNA transcription and replication of this virus. In this study, we collected around 1225 similar compounds of Penciclovir and Acyclovir inhibitors from PubChem and predicted ADME (Adsorption, Distribution, Metabolism and Excretion) molecular descriptors using Swiss-ADME server. Virtually screened 24/1225 compounds based on drug-likeliness five rules (Lipinski, Ghose, Veber, Egan, and Muegge) and lead-likeliness properties. Further 10/24 compounds screened, based on high binding affinity and RMSD<3.5Å against RdRp structure using PyRx docking software. Furthermore, the molecular interactions of 10 compounds studied using Discovery studio software and finally screened five PubChem compounds 57201841, 135408972, 54552823, 135409422 and 467850, based on bioactivity score using Molinsipiration cheminformatics software. All these five compounds showed up anti-SARS CoV-2 activity, though further in-vitro studies are required.