Sequential Optimization Approach Toward an Azapeptide-Based SARS-CoV-2 Main Protease Inhibitor.

ABSTRACT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative agent of the coronavirus disease 2019 (COVID-19), is still circulating and posing a health threat to the global population. Its main protease (M^pro) constitutes an excellent target for the development of antivirals due to its indispensable role in the viral replication cycle. In this work, we employed a sequential approach to identify a potent azapeptide-based M^pro inhibitor. Starting from a series of small-molecule peptidomimetics, identical in their scaffold but equipped with different cysteine-reactive groups, we identified auspicious warheads. The combination of selected moieties with an optimized, previously described P1-P4 azapeptide structure resulted in a potent M^pro inactiv

SUBMITTER: Voget R 

PROVIDER: S-EPMC12723578 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature