title: Mechanisms of Vesicular Stomatitis Virus Inactivation by Protoporphyrin IX, Zinc-Protoporphyrin IX, and Mesoporphyrin IX.
abstract: Virus resistance to antiviral therapies is an increasing concern that makes the development of broad-spectrum antiviral drugs urgent. 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 α-tocopherol partially protected VSV from inactivation by porphyrins, suggesting that singlet oxygen (1O2) was the main reactive oxygen species produced by photoactivation of these molecules. Furthermore,1O2was 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.
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil ccruz@bioqmed.ufrj.br dapoian@bioqmed.ufrj.br.
authors.forename: Christine
authors.identifier: 0000-0003-4838-0703
authors.initials: C
authors.lastname: Cruz-Oliveira
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Andreza F
authors.initials: AF
authors.lastname: Almeida
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: João M
authors.identifier: 0000-0002-8674-0813
authors.initials: JM
authors.lastname: Freire
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marjolly B
authors.initials: MB
authors.lastname: Caruso
authors.affiliation: Centro Nacional de Ressonância Magnética Nuclear, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.|Centro de Desenvolvimento Tecnológico em Saúde, Fiocruz, Rio de Janeiro, Brazil.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Morando
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Vivian N S
authors.initials: VNS
authors.lastname: Ferreira
authors.affiliation: Instituto de Microbiologia Paulo Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Iranaia
authors.initials: I
authors.lastname: Assunção-Miranda
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Andre M O
authors.initials: AMO
authors.lastname: Gomes
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Miguel A R B
authors.initials: MARB
authors.lastname: Castanho
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil ccruz@bioqmed.ufrj.br dapoian@bioqmed.ufrj.br.
authors.forename: Andrea T
authors.initials: AT
authors.lastname: Da Poian
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000737:chemistry; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D024882:Drug Resistance, Viral; D008652:Mesoporphyrins / Q000737:chemistry / Q000494:pharmacology*; D011524:Protoporphyrins / Q000737:chemistry / Q000494:pharmacology*; D026082:Singlet Oxygen / Q000737:chemistry; D019810:Sodium Azide / Q000494:pharmacology; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects*; D038301:Virus Inactivation / Q000187:drug effects; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D000873:Anthracenes; D000998:Antiviral Agents; D008652:Mesoporphyrins; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D026082:Singlet Oxygen; C031468:mesoporphyrin IX; D019810:Sodium Azide; C028025:protoporphyrin IX; C029126:9,10-dimethylanthracene; D024502:alpha-Tocopherol
keywords: photoactivation; porphyrin; singlet oxygen; vesicular stomatitis virus; viral inactivation