Structure-based inhibitor screening of natural products against NSP15 of SARS- CoV-2 revealed Thymopentin and Oleuropein as potent inhibitors

TL;DR

This study used structure-based virtual screening and molecular dynamics to identify natural products, Thymopentin and Oleuropein, as potential inhibitors of SARS-CoV-2 NSP15, suggesting their possible use in COVID-19 treatment.

Contribution

It introduces a computational approach to identify natural product inhibitors targeting NSP15 of SARS-CoV-2, highlighting two promising compounds for further validation.

Findings

Thymopentin and Oleuropein showed high binding affinity to NSP15.

Molecular dynamics confirmed stable binding of these compounds.

Potential for these compounds to reduce SARS-CoV-2 virulence.

Abstract

Coronaviruses are enveloped, non-segmented positive-sense RNA viruses that have the largest genome among RNA viruses. The genome contains a large replicase ORF encodes nonstructural proteins (NSPs), structural and accessory genes. NSP15 is a nidoviral RNA uridylate-specific endoribonuclease (NendoU) has C-terminal catalytic domain. The endoribonuclease activity of NSP15 interferes with the innate immune response of the host. Here, we screened Selleckchem Natural product database of compounds against the NSP15, Thymopentin and Oleuropein showed highest binding energies. The binding of these molecules was further validated by Molecular dynamic simulation and found very stable complexes. These drugs might serve as effective counter molecules in the reduction of virulence of this virus. Future validation of both these inhibitors are worth consideration for patients being treated for COVID -19.