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Exploring the HIV-1 Rev Recognition Element (RRE)-Rev Inhibitory Capacity and Antiretroviral Action of Benfluron Analogs

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dc.contributor.authorChumillas, Sergi
dc.contributor.authorLoharch, Saurabh
dc.contributor.authorBeltran, Manuela
dc.contributor.authorSzewczyk, Mateusz P
dc.contributor.authorBernal, Silvia
dc.contributor.authorPuertas, Maria C
dc.contributor.authorMartinez-Picado, Javier
dc.contributor.authorAlcamí, José
dc.contributor.authorBedoya, Luis M
dc.contributor.authorMarchán, Vicente
dc.contributor.authorGallego, José
dc.contributor.funderGeneralitat Valenciana (España)es_ES
dc.contributor.funderAgencia Estatal de Investigación (España)es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)es_ES
dc.date.accessioned2023-12-15T08:56:57Z
dc.date.available2023-12-15T08:56:57Z
dc.date.issued2023-10-11
dc.description.abstractHuman immunodeficiency virus-type 1 (HIV-1) remains one of the leading contributors to the global burden of disease, and novel antiretroviral agents with alternative mechanisms are needed to cure this infection. Here, we describe an exploratory attempt to optimize the antiretroviral properties of benfluron, a cytostatic agent previously reported to exhibit strong anti-HIV activity likely based on inhibitory actions on virus transcription and Rev-mediated viral RNA export. After obtaining six analogs designed to modify the benzo[c]fluorenone system of the parent molecule, we examined their antiretroviral and toxicity properties together with their capacity to recognize the Rev Recognition Element (RRE) of the virus RNA and inhibit the RRE-Rev interaction. The results indicated that both the benzo[c] and cyclopentanone components of benfluron are required for strong RRE-Rev target engagement and antiretroviral activity and revealed the relative impact of these moieties on RRE affinity, RRE-Rev inhibition, antiviral action and cellular toxicity. These data provide insights into the biological properties of the benzo[c]fluorenone scaffold and contribute to facilitating the design of new anti-HIV agents based on the inhibition of Rev function.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipThis research was funded by Generalitat Valenciana of Spain (PROMETEO 2021/036 grant to J.G. and GRISOLIAP/2020/026 contract to M.P.S.), MCIN/AEI/10.13039/501100011033 of Spain and “ERDF A way of making Europe” (grants PID2020-117508RB-I00 to V.M., RTI2021-093935-B-I00 to J.G., PID2021-125978OB-C2 to J.A. and PID2019-109870RB-I00 and CB21/13/00063 to J.M.-P.).es_ES
dc.format.number20es_ES
dc.format.page7031es_ES
dc.format.volume28es_ES
dc.identifier.citationMolecules. 2023 Oct 11;28(20):7031.es_ES
dc.identifier.doi10.3390/molecules28207031es_ES
dc.identifier.e-issn1420-3049es_ES
dc.identifier.journalMolecules (Basel, Switzerland)es_ES
dc.identifier.pubmedID37894510es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/16809
dc.language.isoenges_ES
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI)es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/PID2020-117508RB-I00es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/RTI2021-093935-B-I00es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/PID2021-125978OB-C2es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/PID2019-109870RB-I00es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/CB21/13/00063es_ES
dc.relation.publisherversionhttps://doi.org/10.3390/molecules28207031es_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAntiviral drug discoveryes_ES
dc.subjectBenflurones_ES
dc.subjectBenzo[c]fluorenonees_ES
dc.subjectHuman immunodeficiency virus type 1es_ES
dc.subjectReves_ES
dc.subjectRNAes_ES
dc.subject.meshHIV-1es_ES
dc.subject.meshAnti-HIV Agentses_ES
dc.subject.meshHIV Infectionses_ES
dc.subject.meshHumanses_ES
dc.subject.meshrev Gene Products, Human Immunodeficiency Viruses_ES
dc.subject.meshRNA, Virales_ES
dc.subject.meshNucleic Acid Conformationes_ES
dc.titleExploring the HIV-1 Rev Recognition Element (RRE)-Rev Inhibitory Capacity and Antiretroviral Action of Benfluron Analogses_ES
dc.typeresearch articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
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