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Review
. 2025 Oct 17;232(Supplement_3):S227-S242.
doi: 10.1093/infdis/jiaf126.

New Developments in Influenza Polymerase Inhibitors

Jingya Li  1 , Yang Jin  1 , Yeming Wang  2 , Lianhan Shang  3 , Bin Cao  2   4
Affiliations
Review

New Developments in Influenza Polymerase Inhibitors

Jingya Li et al. J Infect Dis. .

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.

Keywords: antiviral agents; antiviral resistance; baloxavir; influenza polymerase inhibitors; pharmacokinetics.

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Conflict of interest statement

Potential conflicts of interest. B. C. has served as principal investigator in China for the baloxavir transmission trial sponsored by Roche and as principal investigator of the GP681 phase 2 and phase 3 trials sponsored by Qingfeng Pharmaceutical Group Co, Ltd. Y. W. serves as the sub–principal investigator. Y. W. also discloses receiving compensation as rapporteur for “Optimizing the Clinical Management of Patients” in the 2024 update of the WHO Public Health Research Agenda for Influenza. All other authors report no conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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