In 2019, the huge outbreak of the coronavirus that caused a world-wide pandemic has infected as well as killed thousands of people around the world. Many scientists are looking at natural products as potential inhibitors for the SARS-CoV 2 virus. Natural products, which are the secondary metabolites found in the marine living organisms like sponges have shown promising potential in the creation of novel drugs in the past. Our research investigates a marine natural products database consisting of more than 1,531 compounds to find the possible inhibitors for Papain like protease of SARS-CoV-2 by means of in-silico drug discovery tools offered by Schrdinger’s small molecule drug discovery suite. To perform the task, a virtual screening workflow based on a Structure based Pharmacophore hypothesis created from papain-like protease (PLPro) and inhibitor GRL0617 complex (PDB Code” 7JRN) was followed. The database was first screened based on Lipinski’s Rule of Five followed by Pharmacophore screening, then the screened compounds were taken to the next level of virtual screening workflow and were filtered through an extensive three stage (HTVS, SP and XP) docking. The resulting hits were further evaluated for their ADME properties to confirm their drug likeness. Prime-MMGBSA free energy calculations were also performed on protein-ligand complexes of best hits. Molecular dynamics simulation performed on best hits for 50 ns each has further ascertained the stability of crucial interactions between protein-ligand during the md simulation trajectory. To validate the results in the process, the native ligand along with known drugs proven to work against the virus in clinical trials, were used as positive control.  We found, for the papain-like protease (7JRN) that the marine natural products database contained multiple hit compounds that inhibit the virus better than the known drugs. This shows that marine natural products can be used to help stop the spread of the coronavirus and prevent future deaths.

Pharmacophore based virtual screening of marine natural products to find potential/possible inhibitors of papain-like protease of SARS-CoV-2

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.