In Silico and In Vitro Studies of the Approved Antibiotic Ceftaroline Fosamil and Its Metabolites as Inhibitors of SARS-CoV-2 Replication.

ABSTRACT: The SARS-CoV-2 proteases M^pro and PL^pro are critical targets for antiviral drug development for the treatment of COVID-19. The 1,2,4-thiadiazole functional group is an inhibitor of cysteine proteases, such as papain and cathepsins. This chemical moiety is also present in ceftaroline fosamil (CF), an FDA-approved fifth-generation cephalosporin antibiotic. This study investigates the interactions between CF, its primary metabolites (M1 is dephosphorylated CF and M2 is an opened β-lactam ring) and derivatives (protonated M1H and M2H), and its open 1,2,4-thiadiazole rings derivatives (open-M1H and open-M2H) with SARS-CoV-2 proteases and evaluates CF's effects on in vitro viral replication. In silico analyses (molecular docking and molecular dynamics (MD) simulation

SUBMITTER: Delgado C 

PROVIDER: S-EPMC12031345 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature