In Silico and In Vitro Inhibition of SARS-CoV-2 PLpro with Gramicidin D

Abstract

Finding an effective drug to prevent or treat COVID-19 is of utmost importance in tcurrentpandemic. Since developing a new treatment takes a significant amount of time, drug repurposingcan be an effective option for achieving a rapid response. This study used a combined in silico virtualscreening protocol for candidate SARS-CoV-2 PLpro inhibitors. The Drugbank database was searchedfirst, using the Informational Spectrum Method for Small Molecules, followed by molecular docking.Gramicidin D was selected as a peptide drug, showing the best in silico interaction profile with PLpro.After the expression and purification of PLpro, gramicidin D was screened for protease inhibitionin vitro and was found to be active against PLpro. The current study’s findings are significantbecause it is critical to identify COVID-19 therapies that are efficient, affordable, and have a favorablesafety profile.