Design and In Vitro Evaluation of Novel GC373-like SARS-CoV-2 Main Protease Inhibitors.

ABSTRACT: Significant advances in coronavirus immunoprophylaxis have enabled the control of the SARS-CoV-2 pandemic. However, the continued emergence of SARS-CoV-2 variants with immune escape potential highlights the need for effective direct-acting antivirals targeting conserved viral enzymes. The SARS-CoV-2 main protease (M^pro) remains one of the most promising antiviral drug targets due to its essential role in viral replication and the high conservation of its active site across coronavirus variants. Building upon the established GC373 scaffold, we designed, synthesized, and biochemically evaluated two novel GC373-like peptidomimetic inhibitors incorporated modified glutamine-mimic residues. These analogs were designed to enhance solubility and metabolic resilience while retaining key

SUBMITTER: Kuznetsova AA 

PROVIDER: S-EPMC12939465 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature