Plant-based bioactive molecules for targeting of endoribonuclease using steered molecular dynamic simulation approach: a highly conserved therapeutic target against variants of SARS-CoV-2

Abstract

ABSTRACT The lesser side effects and proven therapeutic efficacy of plant bioactive compounds (phytochemicals) have made them the drug of choice in the current COVID-19 pandemic. The non-structural protein (Nsp-15) also called endoribonuclease is highly conserved in the coronavirus family and is also responsible for modulating host immune response, its inhibition could not only help to reduce present SARS-CoV-2 but also its variants, and is expected to help in generating desired immune response, therefore we chose Nsp-15 as a molecular target for screening phytomolecules. In the present work, multistep molecular docking-based virtual screening methods have been used to screen phytochemicals against the Nsp15. The lead molecules were investigated using steered molecular dynamic simulation followed by molecular dynamics simulations. The results revealed that the protein had well adapted to the ligands as they meet the conditions for the formation of a stable compound. Furthermore, the lead compounds 6-Hydroxyluteolin and Luteolin were found to have low toxicity under physiological settings, better pharmacokinetic properties and strong inhibitory efficacy as observed by ADMET, LE, pKi, and Pi, Pa values. Our results suggest that these compounds can be therapeutically beneficial against SARS-CoV-2; however, more in-vitro and in-vivo investigations are required to substantiate this fact.