New Developments in Influenza Polymerase Inhibitors

Abstract Influenza RNA polymerase is a critical enzyme responsible for viral replication and is highly conserved across different influenza virus strains, making it an ideal target for antivirals. Novel inhibitors targeting its 3 subunits (polymerase basic protein 1, polymerase basic protein 2, and polymerase acidic protein) have been developed and have demonstrated efficacy in clinical trials. The cap-dependent endonuclease inhibitor baloxavir is now widely available and several other polymerase inhibitors are undergoing regulatory review. This review discusses new developments in influenza RNA polymerase inhibitors, including their mechanisms of action, pharmacokinetics, efficacy in preclinical and clinical studies, and the emergence of resistant variants. These new agents offer expanded treatment options, including antiviral combinations, and contribute to enhanced strategies for controlling influenza virus infections.