Structure-Guided Design of Potent Spirocyclic Inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 3C-like Protease.

ABSTRACT: The worldwide impact of the ongoing COVID-19 pandemic on public health has made imperative the discovery and development of direct-acting antivirals aimed at targeting viral and/or host targets. SARS-CoV-2 3C-like protease (3CL^pro) has emerged as a validated target for the discovery of SARS-CoV-2 therapeutics because of the pivotal role it plays in viral replication. We describe herein the structure-guided design of highly potent inhibitors of SARS-CoV-2 3CL^pro that incorporate in their structure novel spirocyclic design elements aimed at optimizing potency by accessing new chemical space. Inhibitors of both SARS-CoV-2 3CL^pro and MERS-CoV 3CL^pro that exhibit nM potency and high safety indices have been identified. The mechanism of action of the i

SUBMITTER: Dampalla CS 

PROVIDER: S-EPMC9172056 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature