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Mechanisms of vesicular stomatitis virus inactivation by protoporphyrin ix, zinc- protoporphyrin ix, and mesoporphyrin ix

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dc.contributor.authorOliveira, Christine Cruz
dc.contributor.authorAlmeida, Andreza F.
dc.contributor.authorFreire, João M.
dc.contributor.authorCaruso, Marjolly B.
dc.contributor.authorMorando, Maria A.
dc.contributor.authorFerreira, Vivian N. S.
dc.contributor.authorMiranda, Iranaia Assunção
dc.contributor.authorGomes, Andre M. O.
dc.contributor.authorCastanho, Miguel A. R. B.
dc.contributor.authorPoian, Andrea T. da
dc.date.accessioned2018-04-05T10:34:13Z
dc.date.available2018-04-05T10:34:13Z
dc.date.issued2017
dc.description© 2017 American Society for Microbiology. All Rights Reserved.pt_PT
dc.description.abstractVirus 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, 1O2 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.pt_PT
dc.description.sponsorshipFundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ; Brazil; grant number E-26/201.167/2014), the Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq; Brazil; grant number 306669/2013-7), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; Brazil; grant number CsF 171/2012), the Fundacao para a Ciencia e Tecnologia-Ministério da Educação e Ciência (FCT-MEC; Portugal; project HIVERA/0002/2013), and Marie Skłodowska-Curie Actions (MSCA; European Commission project INPACT 644167). C.C.-O. acknowledges a Science without Borders postdoctoral fellowship from CAPES (171/2012), and J.M.F. acknowledges an FCT-MEC Ph.D. fellowship (SFRH/BD/70423/2010)pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAntimicrob. Agents Chemother. June 2017 vol. 61 no. 6 e00053-17pt_PT
dc.identifier.doi10.1128/AAC.00053-17pt_PT
dc.identifier.issn0066-4804
dc.identifier.urihttp://hdl.handle.net/10451/32601
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Society for Microbiologypt_PT
dc.relationSTRUCTURAL PROTEINS OF ENVELOPED VIRUS: FROM BIOCHEMISTRY TO MOLECULAR MEDICINE. A FOCUS ON DENGUE HEMORRHAGIC FEVER VIRUS
dc.relation.publisherversionhttp://aac.asm.org/pt_PT
dc.subjectPhotoactivationpt_PT
dc.subjectPorphyrinpt_PT
dc.subjectSinglet oxygenpt_PT
dc.subjectVesicular stomatitis viruspt_PT
dc.subjectViral inactivationpt_PT
dc.titleMechanisms of vesicular stomatitis virus inactivation by protoporphyrin ix, zinc- protoporphyrin ix, and mesoporphyrin ixpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleSTRUCTURAL PROTEINS OF ENVELOPED VIRUS: FROM BIOCHEMISTRY TO MOLECULAR MEDICINE. A FOCUS ON DENGUE HEMORRHAGIC FEVER VIRUS
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/HIVERA%2F0002%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F70423%2F2010/PT
oaire.citation.issue6pt_PT
oaire.citation.titleAntimicrobial Agents and Chemotherapypt_PT
oaire.citation.volume61pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamOE
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationf992a355-2673-47ed-9b17-13d4e6cd4d88
relation.isProjectOfPublication740ee52c-b5d2-4811-9651-6283006aebee
relation.isProjectOfPublication.latestForDiscoveryf992a355-2673-47ed-9b17-13d4e6cd4d88

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