Repurposing HIV Protease Inhibitors Atazanavir and Darunavir as Antifungal Treatments against Candida albicans Infections: An In Vitro and In Vivo Study

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dc.contributor.authorFenley, Juliana de C. [UNESP]
dc.contributor.authorde Barros, Patrícia P. [UNESP]
dc.contributor.authorCarmo, Paulo H. F. do [UNESP]
dc.contributor.authorGarcia, Maíra T. [UNESP]
dc.contributor.authorRossoni, Rodnei D. [UNESP]
dc.contributor.authorJunqueira, Juliana C. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionFederal University of Rio Grande do Norte (UFRN)
dc.date.accessioned2023-07-29T15:13:51Z
dc.date.available2023-07-29T15:13:51Z
dc.date.issued2022-11-01
dc.description.abstractCandida albicans is the chief etiological agent of candidiasis, a mycosis prevalent in individuals with acquired immunodeficiency syndrome (AIDS). In recent years, the introduction of human immunodeficiency virus (HIV) protease inhibitors (HIV-PI) has reduced the prevalence of candidiasis in these patients. Seeking new therapeutic strategies based on the perspective of drug repositioning, we evaluated the effects of two second-generation HIV-PIs, atazanavir (ATV) and darunavir (DRV), on virulence factors of C. albicans and experimental candidiasis. For this, clinical strains of C. albicans were subjected to in vitro and in vivo treatments with ATV or DRV. As a result, ATV and DRV exhibited antifungal activity against fungal cells at 512 μg/mL, reduced the viability and biomass of biofilms, and inhibited filamentation of C. albicans. In addition, these HIV-PIs downregulated the expression of SAP2 and BRC1 genes of C. albicans. In an in vivo study, prophylactic use of ATV and DRV prolonged the survival rate of Galleria mellonella larvae infected with C. albicans. Therefore, ATV and DRV showed activity against C. albicans by reducing cell growth, biofilm formation, filamentation, and expression of virulence genes. Furthermore, ATV and DRV decreased experimental candidiasis, suggesting the repurposing of HIV-PIs as antifungal treatments for C. albicans infections.en
dc.description.affiliationDepartment of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (Unesp), São Paulo
dc.description.affiliationMulticampi School of Medical Sciences Federal University of Rio Grande do Norte (UFRN), Rio Grande do Norte
dc.description.affiliationUnespDepartment of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (Unesp), São Paulo
dc.format.extent5379-5389
dc.identifierhttp://dx.doi.org/10.3390/cimb44110364
dc.identifier.citationCurrent Issues in Molecular Biology, v. 44, n. 11, p. 5379-5389, 2022.
dc.identifier.doi10.3390/cimb44110364
dc.identifier.issn1467-3045
dc.identifier.issn1467-3037
dc.identifier.scopus2-s2.0-85141619011
dc.identifier.urihttp://hdl.handle.net/11449/249358
dc.language.isoeng
dc.relation.ispartofCurrent Issues in Molecular Biology
dc.sourceScopus
dc.subjectatazanavir sulfate
dc.subjectCandida albicans
dc.subjectdarunavir
dc.subjectHIV
dc.subjectprotease inhibitors
dc.subjectvirulence factors
dc.titleRepurposing HIV Protease Inhibitors Atazanavir and Darunavir as Antifungal Treatments against Candida albicans Infections: An In Vitro and In Vivo Studyen
dc.typeArtigo
unesp.author.orcid0000-0003-4885-2811[2]
unesp.author.orcid0000-0003-3186-885X[3]
unesp.author.orcid0000-0002-9977-3040[5]
unesp.author.orcid0000-0001-6646-6856[6]

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