{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:56:45Z","timestamp":1790791005145,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,2,25]],"date-time":"2024-02-25T00:00:00Z","timestamp":1708819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Antiviral therapy based on neuraminidase (oseltamivir) or polymerase (baloxavir marboxil) inhibitors plays an important role in the management of influenza infections. However, the emergence of drug resistance and the uncontrolled inflammatory response are major limitations in the treatment of severe influenza disease. Protectins D1 (PD1) and DX (PDX), part of a family of pro\u2010resolving mediators, have previously demonstrated anti\u2010influenza activity as well as anti\u2010inflammatory properties in various clinical contexts. Herein, we synthetized a series of simplified PDX analogs and assessed their in vitro antiviral activity against influenza A(H1N1) viruses, including oseltamivir\u2010 and baloxavir\u2010resistant variants. In ST6GalI\u2010MDCK cells, the PDX analog AN\u2010137B reduced viral replication in a dose\u2010dependent manner with IC<jats:sub>50<\/jats:sub> values of 23.8 for A\/Puerto Rico\/8\/1934 (H1N1) and between 32.6 and 36.7\u2009\u00b5M for susceptible and resistant A(H1N1)pdm09 viruses. In MTS\u2010based cell viability experiments, AN\u2010137B showed a 50% cellular cytotoxicity (CC<jats:sub>50<\/jats:sub>) of 638.7\u2009\u00b5M with a resulting selectivity index of 26.8. Of greater importance, the combination of AN\u2010137B with oseltamivir or baloxavir resulted in synergistic and additive in vitro effects, respectively. Treatment of lipopolysaccharide (LPS)\u2010stimulated macrophages with AN\u2010137B resulted in a decrease of iNOS activity as shown by the reduction of nitrite production, suggesting an anti\u2010inflammatory effect. In conclusion, our results indicate that the protectin analog AN\u2010137B constitutes an interesting therapeutic modality against influenza A virus, warranting further evaluation in animal models.<\/jats:p>","DOI":"10.1002\/jmv.29484","type":"journal-article","created":{"date-parts":[[2024,2,25]],"date-time":"2024-02-25T13:34:34Z","timestamp":1708868074000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A protectin DX (PDX) analog with in vitro activity against influenza A(H1N1) viruses"],"prefix":"10.1002","volume":"96","author":[{"given":"Nicolas","family":"Fortin","sequence":"first","affiliation":[{"name":"Research Center in Infectious Diseases CHU de Qu\u00e9bec\u2010Universit\u00e9 Laval Quebec City Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"H\u00e9naut","sequence":"additional","affiliation":[{"name":"Research Center in Infectious Diseases CHU de 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