Repurposing 1,2,4-oxadiazoles as SARS-CoV-2 PLpro inhibitors and investigation of their possible viral entry blockade potential.

ABSTRACT: Although vaccines are obviously mitigating the COVID-19 pandemic diffusion, efficient complementary antiviral agents are urgently needed to combat SARS-CoV-2. The viral papain-like protease (PLpro) is a promising therapeutic target being one of only two essential proteases crucial for viral replication. Nevertheless, it dysregulates the host immune sensing response. Here we report repositioning of the privileged 1,2,4-oxadiazole scaffold as promising SARS-CoV-2 PLpro inhibitor with potential viral entry inhibition profile. The design strategy relied on mimicking the general structural features of the lead benzamide PLpro inhibitor GRL0617 with isosteric replacement of its pharmacophoric amide backbone by 1,2,4-oxadiazole core. Inspired by the multitarget antiviral agents, the substitution

SUBMITTER: Ayoup MS 

PROVIDER: S-EPMC10008816 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature