Dual Inhibitors of Main Protease (M^Pro) and Cathepsin L as Potent Antivirals against SARS-CoV2.

ABSTRACT: Given the current impact of SARS-CoV2 and COVID-19 on human health and the global economy, the development of direct acting antivirals is of paramount importance. Main protease (M^Pro), a cysteine protease that cleaves the viral polyprotein, is essential for viral replication. Therefore, M^Pro is a novel therapeutic target. We identified two novel M^Pro inhibitors, D-FFRCMKyne and D-FFCitCMKyne, that covalently modify the active site cysteine (C145) and determined cocrystal structures. Medicinal chemistry efforts led to SM141 and SM142, which adopt a unique binding mode within the M^Pro active site. Notably, these inhibitors do not inhibit the other cysteine protease, papain-like protease (PL^Pro), involved in the life cycle o

SUBMITTER: Mondal S 

PROVIDER: S-EPMC9662648 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature