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PV displayed antiviral efficacy against SARS\u2010CoV\u20102 and influenza A viruses H1N1 and H5N1 in single infection as well as in co\u2010infection. We demonstrated PV's activity against various SARS\u2010CoV\u20102 variants and identified its action at the post\u2010entry stage of the viral life cycle. Notably, treatment of air\u2010liquid interface (ALI) cultures of primary bronchial epithelial cells with PV significantly inhibited SARS\u2010CoV\u20102 levels. Additionally, PV was found to attenuate interferon (IFN) signaling independently of viral infection. Mechanistically, PV decreased the activation of the IFN\u2010stimulated response element following stimulation with all three IFN types by suppressing STAT1 and STAT2 phosphorylation and nuclear translocation. Furthermore, the combination of PV with approved COVID\u201019 therapeutics molnupiravir and remdesivir demonstrated synergistic effects. Given its immunomodulatory effects and clinical availability, PV shows promising potential as a component for combination therapy against COVID\u201019.<\/jats:p>","DOI":"10.1002\/jmv.70319","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T07:44:44Z","timestamp":1743752684000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Papaverine Targets STAT Signaling: A Dual\u2010Action Therapy Option Against SARS\u2010CoV\u20102"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4457-6680","authenticated-orcid":false,"given":"Philipp","family":"Reus","sequence":"first","affiliation":[{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, ScreeningPort Hamburg Germany"},{"name":"Institute for Medical Virology, University Hospital, Goethe University Frankfurt Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Torbica","sequence":"additional","affiliation":[{"name":"Institute for Medical Virology, University Hospital, Goethe University Frankfurt Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Rothenburger","sequence":"additional","affiliation":[{"name":"Institute for Medical Virology, University Hospital, Goethe University Frankfurt Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Bechtel","sequence":"additional","affiliation":[{"name":"Institute for Medical Virology, University Hospital, Goethe University Frankfurt Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Kandler","sequence":"additional","affiliation":[{"name":"Institute for Medical Virology, University Hospital, Goethe University Frankfurt Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Ciesek","sequence":"additional","affiliation":[{"name":"Institute for Medical Virology, University Hospital, Goethe University Frankfurt Frankfurt Germany"},{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Gribbon","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, ScreeningPort Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimo","family":"Kannt","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jindrich","family":"Cinatl","sequence":"additional","affiliation":[{"name":"Institute for Medical Virology, University Hospital, Goethe University Frankfurt Frankfurt Germany"},{"name":"Dr. Petra Joh Research Institute Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisa","family":"Bojkova","sequence":"additional","affiliation":[{"name":"Institute for Medical Virology, University Hospital, Goethe University Frankfurt Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"E.Mathieu H.Ritchie L.Rod\u00e9s\u2010Guirao et al. 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