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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.<\/jats:p>","DOI":"10.1093\/infdis\/jiaf126","type":"journal-article","created":{"date-parts":[[2025,3,22]],"date-time":"2025-03-22T23:53:51Z","timestamp":1742687631000},"page":"S227-S242","source":"Crossref","is-referenced-by-count":10,"title":["New Developments in Influenza Polymerase Inhibitors"],"prefix":"10.1093","volume":"232","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1255-447X","authenticated-orcid":false,"given":"Jingya","family":"Li","sequence":"first","affiliation":[{"name":"School of Medicine, Tsinghua Medicine, Tsinghua University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Medicine, Tsinghua Medicine, Tsinghua University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeming","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Capital Medical University, National Center for Respiratory Medicine , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianhan","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology of Microbial Diseases, Yale School of Public Health , New Haven, Connecticut ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Capital Medical University, National Center for Respiratory Medicine , Beijing ,","place":["China"]},{"name":"Tsinghua University\u2013Peking University Joint Center for Life Sciences , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"2025101622264863200_jiaf126-B1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1086\/518936","article-title":"Surveillance of resistance to adamantanes among influenza A(H3N2) and A(H1N1) viruses isolated worldwide","volume":"196","author":"Deyde","year":"2007","journal-title":"J Infect 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