Structural insights of the coronavirus main protease in complex with the non-covalent inhibitor CCF0058981.

ABSTRACT: The highly pathogenic SARS-CoV-2 causes COVID-19, which threatens global public health and socio-economic stability through persistent transmission and mutation. Effective therapeutics against SARS-CoV-2 and its variants are urgently needed. The main protease (M^pro), highly conserved among coronaviruses and lacking human homologs, is pivotal for viral replication, making it an attractive antiviral target. CCF0058981, a novel non-covalent inhibitor developed based on the ML300 scaffold, demonstrates potent low-nanomolar inhibitory activity against SARS-CoV-2 M^pro and sub-micromolar antiviral efficacy against SARS-CoV-2. Its non-covalent binding mechanism effectively mitigates the off-target risks commonly associated with traditional covalent inhibitors, thereby providi

SUBMITTER: Zeng P 

PROVIDER: S-EPMC12818112 | biostudies-literature | 2026 Jun

REPOSITORIES: biostudies-literature