{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:19:08Z","timestamp":1791875948015,"version":"4.3.4"},"reference-count":45,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU","award":["PE00000007"],"award-info":[{"award-number":["PE00000007"]}]},{"name":"EU","award":["INF-ACT"],"award-info":[{"award-number":["INF-ACT"]}]},{"name":"EU","award":["PAR FSC INFRA-P2 B COVID"],"award-info":[{"award-number":["PAR FSC INFRA-P2 B COVID"]}]},{"name":"Piedmont Region","award":["PE00000007"],"award-info":[{"award-number":["PE00000007"]}]},{"name":"Piedmont Region","award":["INF-ACT"],"award-info":[{"award-number":["INF-ACT"]}]},{"name":"Piedmont Region","award":["PAR FSC INFRA-P2 B COVID"],"award-info":[{"award-number":["PAR FSC INFRA-P2 B COVID"]}]},{"name":"University of Torino","award":["PE00000007"],"award-info":[{"award-number":["PE00000007"]}]},{"name":"University of Torino","award":["INF-ACT"],"award-info":[{"award-number":["INF-ACT"]}]},{"name":"University of Torino","award":["PAR FSC INFRA-P2 B COVID"],"award-info":[{"award-number":["PAR FSC INFRA-P2 B COVID"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The appearance of new respiratory virus infections in humans with epidemic or pandemic potential has underscored the urgent need for effective broad-spectrum antivirals (BSAs). Bioactive compounds derived from plants may provide a natural source of new BSA candidates. Here, we investigated the novel phytocomplex formulation SP4\u2122 as a candidate direct-acting BSA against major current human respiratory viruses, including coronaviruses and influenza viruses. SP4\u2122 inhibited the in vitro replication of SARS-CoV-2, hCoV-OC43, hCoV-229E, Influenza A and B viruses, and respiratory syncytial virus in the low-microgram range. Using hCoV-OC43 as a representative respiratory virus, most of the antiviral activity of SP4\u2122 was observed to stem primarily from its dimeric A-type proanthocyanidin (PAC-A) component. Further investigations of the mechanistic mode of action showed SP4\u2122 and its PAC-A-rich fraction to prevent hCoV-OC43 from attaching to target cells and exert virucidal activity. This occurred through their interaction with the spike protein of hCoV-OC43 and SARS-CoV-2, thereby interfering with spike functions and leading to the loss of virion infectivity. Overall, these findings support the further development of SP4\u2122 as a candidate BSA of a natural origin for the prevention of human respiratory virus infections.<\/jats:p>","DOI":"10.3390\/ijms25137370","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T12:21:03Z","timestamp":1720441263000},"page":"7370","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Novel A-Type Proanthocyanidin-Rich Phytocomplex SP4\u2122 Acts as a Broad-Spectrum Antiviral Agent against Human Respiratory Viruses"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2869-357X","authenticated-orcid":false,"given":"Giulia","family":"Sibille","sequence":"first","affiliation":[{"name":"Microbiology and Virology Unit, Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0047-978X","authenticated-orcid":false,"given":"Giuseppe","family":"Mannino","sequence":"additional","affiliation":[{"name":"Plant Physiology Unit, Department of Life Sciences and Systems Biology, University of Torino, Via Quarello 15\/a, 10135 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5135-5707","authenticated-orcid":false,"given":"Ilaria","family":"Frasson","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Padova, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8004-1001","authenticated-orcid":false,"given":"Marta","family":"Pavan","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Unit, Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4256-5774","authenticated-orcid":false,"given":"Anna","family":"Luganini","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Unit, Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5136-7406","authenticated-orcid":false,"given":"Cristiano","family":"Salata","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Padova, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6814-2353","authenticated-orcid":false,"given":"Massimo E.","family":"Maffei","sequence":"additional","affiliation":[{"name":"Plant Physiology Unit, Department of Life Sciences and Systems Biology, University of Torino, Via Quarello 15\/a, 10135 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1583-9146","authenticated-orcid":false,"given":"Giorgio","family":"Gribaudo","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Unit, Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1111\/bcp.14859","article-title":"Blueprint for pandemic response: Focus on translational medicine, clinical pharmacology and pharmacometrics","volume":"87","author":"Davda","year":"2021","journal-title":"Br. 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