{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T15:30:05Z","timestamp":1782487805763,"version":"3.54.5"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T00:00:00Z","timestamp":1684540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"MEXT","doi-asserted-by":"publisher","award":["16H06429"],"award-info":[{"award-number":["16H06429"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"MEXT","doi-asserted-by":"publisher","award":["16K21723"],"award-info":[{"award-number":["16K21723"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"MEXT","doi-asserted-by":"publisher","award":["16H06434"],"award-info":[{"award-number":["16H06434"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS","doi-asserted-by":"publisher","award":["18KO7140"],"award-info":[{"award-number":["18KO7140"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","award":["HHSN272201400008C"],"award-info":[{"award-number":["HHSN272201400008C"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Widespread resistance of influenza viruses to neuraminidase (NA) inhibitor or polymerase inhibitor, baloxavir, is a major public health concern. The amino acid mutations R152K in NA and I38T in polymerase acidic (PA) are responsible for resistance to NA inhibitors and baloxavir, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We generated recombinant A(H1N1)pdm09 viruses possessing NA-R152K, PA-I38T or both mutations by using a plasmid-based reverse genetics system, characterized their virological properties in vitro and in vivo, and examined whether oseltamivir, baloxavir and favipiravir are effective against these mutant viruses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The three mutant viruses showed similar or superior growth kinetics and virulence to those of wild-type virus. Although oseltamivir and baloxavir blocked the replication of the wild-type virus in vitro, oseltamivir and baloxavir failed to suppress the replication of the NA-R152K and PA-I38T viruses in vitro, respectively. Mutant virus possessing both mutations grew in the presence of oseltamivir or baloxavir in vitro. Baloxavir treatment protected mice from lethal infection with wild-type or NA-R152K virus, but failed to protect mice from lethal infection with PA-I38T or PA-I38T\/NA-R152K virus. Favipiravir treatment protected mice from lethal infection with all viruses tested, whereas oseltamivir treatment did not protect at all.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our findings indicate that favipiravir should be used to treat patients with suspected baloxavir-resistant virus infection.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkad145","type":"journal-article","created":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T21:50:03Z","timestamp":1684619403000},"page":"1649-1657","source":"Crossref","is-referenced-by-count":5,"title":["Efficacy of favipiravir against influenza virus resistant to both baloxavir and neuraminidase inhibitors"],"prefix":"10.1093","volume":"78","author":[{"given":"Maki","family":"Kiso","sequence":"first","affiliation":[{"name":"Division of Virology, Institute of Medical Science, University of Tokyo , Tokyo , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7768-5157","authenticated-orcid":false,"given":"Seiya","family":"Yamayoshi","sequence":"additional","affiliation":[{"name":"Division of Virology, Institute of Medical Science, University of Tokyo , Tokyo , Japan"},{"name":"International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo , Tokyo , Japan"},{"name":"Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute , Tokyo , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Kawaoka","sequence":"additional","affiliation":[{"name":"Division of Virology, Institute of Medical Science, University of Tokyo , Tokyo , Japan"},{"name":"Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute , Tokyo , Japan"},{"name":"Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin\u2013Madison , Madison WI , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,20]]},"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/78\/7\/1649\/50792377\/dkad145.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/78\/7\/1649\/50792377\/dkad145.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T07:58:15Z","timestamp":1688543895000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/78\/7\/1649\/7174982"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,20]]},"references-count":0,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,5,20]]},"published-print":{"date-parts":[[2023,7,5]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkad145","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,7]]},"published":{"date-parts":[[2023,5,20]]}}}