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Targeting of the viral envelope, a component shared by a large number of viruses, emerges as a promising strategy to overcome this problem. Natural and synthetic porphyrins are good candidates for antiviral development due to their relative hydrophobicity and pro-oxidant character. In the present work, we characterized the antiviral activities of protoprophyrin IX (PPIX), Zn-protoporphyrin IX (ZnPPIX), and mesoporphyrin IX (MPIX) against vesicular stomatitis virus (VSV) and evaluated the mechanisms involved in this activity. Treatment of VSV with PPIX, ZnPPIX, and MPIX promoted dose-dependent virus inactivation, which was potentiated by porphyrin photoactivation. All three porphyrins inserted into lipid vesicles and disturbed the viral membrane organization. In addition, the porphyrins also affected viral proteins, inducing VSV glycoprotein cross-linking, which was enhanced by porphyrin photoactivation. Virus incubation with sodium azide and \u03b1-tocopherol partially protected VSV from inactivation by porphyrins, suggesting that singlet oxygen (\n            <jats:sup>1<\/jats:sup>\n            O\n            <jats:sub>2<\/jats:sub>\n            ) was the main reactive oxygen species produced by photoactivation of these molecules. Furthermore,\n            <jats:sup>1<\/jats:sup>\n            O\n            <jats:sub>2<\/jats:sub>\n            was detected by 9,10-dimethylanthracene oxidation in photoactivated porphyrin samples, reinforcing this hypothesis. These results reveal the potential therapeutic application of PPIX, ZnPPIX, and MPIX as good models for broad antiviral drug design.\n          <\/jats:p>","DOI":"10.1128\/aac.00053-17","type":"journal-article","created":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T00:40:52Z","timestamp":1490661652000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":39,"title":["Mechanisms of Vesicular Stomatitis Virus Inactivation by Protoporphyrin IX, Zinc-Protoporphyrin IX, and Mesoporphyrin IX"],"prefix":"10.1128","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4838-0703","authenticated-orcid":false,"given":"Christine","family":"Cruz-Oliveira","sequence":"first","affiliation":[{"name":"Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreza F.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8674-0813","authenticated-orcid":false,"given":"Jo\u00e3o M.","family":"Freire","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolly B.","family":"Caruso","sequence":"additional","affiliation":[{"name":"Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Morando","sequence":"additional","affiliation":[{"name":"Centro Nacional de Resson\u00e2ncia Magn\u00e9tica Nuclear, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"},{"name":"Centro de Desenvolvimento Tecnol\u00f3gico em Sa\u00fade, Fiocruz, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian N. S.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iranaia","family":"Assun\u00e7\u00e3o-Miranda","sequence":"additional","affiliation":[{"name":"Instituto de Microbiologia Paulo G\u00f3es, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre M. O.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A. R. 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