{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:24:44Z","timestamp":1790738684677,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (Inserm), Fondation pour la Recherche M\u00e9dicale (Programme \u00ab \u00e9quipe FRM 2021 \u00bb), Inserm Transfert (COPOC), Agence Nationale de la Recherche","award":["ANR-20-COV5-0004"],"award-info":[{"award-number":["ANR-20-COV5-0004"]}]},{"name":"Institut national de recherche pour l\u2019agriculture, l\u2019alimentation et l\u2019environnement (INRAE) and the French Minist\u00e8re de l\u2019Agriculture","award":["ANR-20-COV5-0004"],"award-info":[{"award-number":["ANR-20-COV5-0004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The exceptional impact of the COVID-19 pandemic has stimulated an intense search for antiviral molecules. Host-targeted antiviral molecules have the potential of presenting broad-spectrum antiviral activity and are also considered as less likely to select for resistant viruses. In this study, we investigated the antiviral activity exerted by AM-001, a specific pharmacological inhibitor of EPAC1, a host exchange protein directly activated by cyclic AMP (cAMP). The cAMP-sensitive protein, EPAC1 regulates various physiological and pathological processes but its role in SARS-CoV-2 and influenza A virus infection has not yet been studied. Here, we provide evidence that the EPAC1 specific inhibitor AM-001 exerts potent antiviral activity against SARS-CoV-2 in the human lung Calu-3 cell line and the African green monkey Vero cell line. We observed a concentration-dependent inhibition of SARS-CoV-2 infectious viral particles and viral RNA release in the supernatants of AM-001 treated cells that was not associated with a significant impact on cellular viability. Furthermore, we identified AM-001 as an inhibitor of influenza A virus in Calu-3 cells. Altogether these results identify EPAC1 inhibition as a promising therapeutic target against viral infections.<\/jats:p>","DOI":"10.3390\/v15020319","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T03:26:41Z","timestamp":1674444401000},"page":"319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["EPAC1 Pharmacological Inhibition with AM-001 Prevents SARS-CoV-2 and Influenza A Virus Replication in Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2086-9347","authenticated-orcid":false,"given":"Charlotte","family":"Foret-Lucas","sequence":"first","affiliation":[{"name":"Ecole Nationale V\u00e9t\u00e9rinaire de Toulouse, Universit\u00e9 de Toulouse, ENVT, INRAE, IHAP, UMR 1225, 31300 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Figueroa","sequence":"additional","affiliation":[{"name":"Ecole Nationale V\u00e9t\u00e9rinaire de Toulouse, Universit\u00e9 de Toulouse, ENVT, INRAE, IHAP, UMR 1225, 31300 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Bertin","sequence":"additional","affiliation":[{"name":"Ecole Nationale V\u00e9t\u00e9rinaire de Toulouse, Universit\u00e9 de Toulouse, ENVT, INRAE, IHAP, UMR 1225, 31300 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5657-0027","authenticated-orcid":false,"given":"Pierre","family":"Bessi\u00e8re","sequence":"additional","affiliation":[{"name":"Ecole Nationale V\u00e9t\u00e9rinaire de Toulouse, Universit\u00e9 de Toulouse, ENVT, INRAE, IHAP, UMR 1225, 31300 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Lucas","sequence":"additional","affiliation":[{"name":"Institute of Metabolic and Cardiovascular Diseases, INSERM, Universit\u00e9 de Toulouse, UMR 1297-I2MC, 31432 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorian","family":"Bergonnier","sequence":"additional","affiliation":[{"name":"Institute of Metabolic and Cardiovascular Diseases, INSERM, Universit\u00e9 de Toulouse, UMR 1297-I2MC, 31432 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5054-3634","authenticated-orcid":false,"given":"Marine","family":"Wasniewski","sequence":"additional","affiliation":[{"name":"Nancy Laboratory for Rabies and Wildlife, ANSES, Lyssavirus Unit, 54220 Malz\u00e9ville, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4753-6614","authenticated-orcid":false,"given":"Alexandre","family":"Servat","sequence":"additional","affiliation":[{"name":"Nancy Laboratory for Rabies and Wildlife, ANSES, Lyssavirus Unit, 54220 Malz\u00e9ville, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7053-2203","authenticated-orcid":false,"given":"Arnaud","family":"Tessier","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CNRS, CEISAM, UMR 6230, 44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5239-6017","authenticated-orcid":false,"given":"Frank","family":"Lezoualc\u2019h","sequence":"additional","affiliation":[{"name":"Institute of Metabolic and Cardiovascular Diseases, INSERM, Universit\u00e9 de Toulouse, UMR 1297-I2MC, 31432 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Volmer","sequence":"additional","affiliation":[{"name":"Ecole Nationale V\u00e9t\u00e9rinaire de Toulouse, Universit\u00e9 de Toulouse, ENVT, INRAE, IHAP, UMR 1225, 31300 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1016\/S0140-6736(22)01585-9","article-title":"The Lancet Commission on Lessons for the Future from the COVID-19 Pandemic","volume":"400","author":"Sachs","year":"2022","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zheng, Y., Li, S., Song, K., Ye, J., Li, W., Zhong, Y., Feng, Z., Liang, S., Cai, Z., and Xu, K. 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