{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:38:44Z","timestamp":1790419124429,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T00:00:00Z","timestamp":1602115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["229733"],"award-info":[{"award-number":["229733"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Two antiviral classes, the neuraminidase inhibitors (NAIs) and polymerase inhibitors (baloxavir marboxil and favipiravir) can be used to prevent and treat influenza infections during seasonal epidemics and pandemics. However, prolonged treatment may lead to the emergence of drug resistance. Therapeutic combinations constitute an alternative to prevent resistance and reduce antiviral doses. Therefore, we evaluated in vitro combinations of baloxavir acid (BXA) and other approved drugs against influenza A(H1N1)pdm09 and A(H3N2) subtypes. The determination of an effective concentration inhibiting virus cytopathic effects by 50% (EC50) for each drug and combination indexes (CIs) were based on cell viability. CompuSyn software was used to determine synergism, additivity or antagonism between drugs. Combinations of BXA and NAIs or favipiravir had synergistic effects on cell viability against the two influenza A subtypes. Those effects were confirmed using a physiological and predictive ex vivo reconstructed human airway epithelium model. On the other hand, the combination of BXA and ribavirin showed mixed results. Overall, BXA stands as a good candidate for combination with several existing drugs, notably oseltamivir and favipiravir, to improve in vitro antiviral activity. These results should be considered for further animal and clinical evaluations.<\/jats:p>","DOI":"10.3390\/v12101139","type":"journal-article","created":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T08:52:41Z","timestamp":1602147161000},"page":"1139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses"],"prefix":"10.3390","volume":"12","author":[{"given":"Liva","family":"Checkmahomed","sequence":"first","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec\u2014Centre Hospitalier de l\u2019Universit\u00e9 Laval (CHUQ-CHUL) and Laval University, Qu\u00e9bec City, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2159-6507","authenticated-orcid":false,"given":"Blandine","family":"Padey","sequence":"additional","affiliation":[{"name":"CIRI\u2014Centre International de Recherche en Infectiologie, (Team VirPath), University Lyon, Inserm U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS\u2014Centre National de la Recherche Scientifique UMR5308, ENS de Lyon, F-69007 Lyon, France"},{"name":"Signia Therapeutics SAS, 69100 Villeurbane, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0918-6804","authenticated-orcid":false,"given":"Andr\u00e9s","family":"Pizzorno","sequence":"additional","affiliation":[{"name":"CIRI\u2014Centre International de Recherche en Infectiologie, (Team VirPath), University Lyon, Inserm U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS\u2014Centre National de la Recherche Scientifique UMR5308, ENS de Lyon, F-69007 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9393-7684","authenticated-orcid":false,"given":"Olivier","family":"Terrier","sequence":"additional","affiliation":[{"name":"CIRI\u2014Centre International de Recherche en Infectiologie, (Team VirPath), University Lyon, Inserm U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS\u2014Centre National de la Recherche Scientifique UMR5308, ENS de Lyon, F-69007 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Rosa-Calatrava","sequence":"additional","affiliation":[{"name":"CIRI\u2014Centre International de Recherche en Infectiologie, (Team VirPath), University Lyon, Inserm U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS\u2014Centre National de la Recherche Scientifique UMR5308, ENS de Lyon, F-69007 Lyon, France"},{"name":"VirNext, Facult\u00e9 de M\u00e9decine RTH Laennec, Universit\u00e9 Claude Bernard Lyon 1, Universit\u00e9 de Lyon, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yacine","family":"Abed","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec\u2014Centre Hospitalier de l\u2019Universit\u00e9 Laval (CHUQ-CHUL) and Laval University, Qu\u00e9bec City, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Baz","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec\u2014Centre Hospitalier de l\u2019Universit\u00e9 Laval (CHUQ-CHUL) and Laval University, Qu\u00e9bec City, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Boivin","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec\u2014Centre Hospitalier de l\u2019Universit\u00e9 Laval (CHUQ-CHUL) and Laval University, Qu\u00e9bec City, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1111\/irv.12570","article-title":"65 years of influenza surveillance by a World Health Organization-coordinated global network","volume":"12","author":"Ziegler","year":"2018","journal-title":"Influenza Other Respir. 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