dc.contributor.author | Raïch-Regué, Dalia | |
dc.contributor.author | Tenorio, Raquel | |
dc.contributor.author | Fernández de Castro, Isabel | |
dc.contributor.author | Tarrés-Freixas, Ferran | |
dc.contributor.author | Sachse, Martin | |
dc.contributor.author | Perez-Zsolt, Daniel | |
dc.contributor.author | Muñoz-Basagoiti, Jordana | |
dc.contributor.author | Fernández-Sánchez, Sara Y | |
dc.contributor.author | Gallemí, Marçal | |
dc.contributor.author | Ortega-González, Paula | |
dc.contributor.author | Fernández-Oliva, Alberto | |
dc.contributor.author | Gabaldón, José A | |
dc.contributor.author | Nuñez-Delicado, Estrella | |
dc.contributor.author | Casas, Josefina | |
dc.contributor.author | Roca, Núria | |
dc.contributor.author | Cantero, Guillermo | |
dc.contributor.author | Pérez, Mónica | |
dc.contributor.author | Usai, Carla | |
dc.contributor.author | Lorca-Oró, Cristina | |
dc.contributor.author | Alert, Júlia-Vergara | |
dc.contributor.author | Segalés, Joaquim | |
dc.contributor.author | Carrillo, Jorge | |
dc.contributor.author | Blanco, Julià | |
dc.contributor.author | Clotet Sala, Bonaventura | |
dc.contributor.author | Cerón-Carrasco, José P | |
dc.contributor.author | Izquierdo-Useros, Nuria | |
dc.contributor.author | Risco, Cristina | |
dc.date.accessioned | 2023-12-15T19:47:02Z | |
dc.date.available | 2023-12-15T19:47:02Z | |
dc.date.issued | 2023-08 | |
dc.identifier.citation | Biomed Pharmacother. 2023 Aug:164:114997. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/16824 | |
dc.description.abstract | The SARS-CoV-2 pandemic made evident that there are only a few drugs against coronavirus. Here we aimed to identify a cost-effective antiviral with broad spectrum activity and high safety profile. Starting from a list of 116 drug candidates, we used molecular modelling tools to rank the 44 most promising inhibitors. Next, we tested their efficacy as antivirals against α and β coronaviruses, such as the HCoV-229E and SARS-CoV-2 variants. Four drugs, OSW-1, U18666A, hydroxypropyl-β-cyclodextrin (HβCD) and phytol, showed in vitro antiviral activity against HCoV-229E and SARS-CoV-2. The mechanism of action of these compounds was studied by transmission electron microscopy and by fusion assays measuring SARS-CoV-2 pseudoviral entry into target cells. Entry was inhibited by HβCD and U18666A, yet only HβCD inhibited SARS-CoV-2 replication in the pulmonary Calu-3 cells. Compared to the other cyclodextrins, β-cyclodextrins were the most potent inhibitors, which interfered with viral fusion via cholesterol depletion. β-cyclodextrins also prevented infection in a human nasal epithelium model ex vivo and had a prophylactic effect in the nasal epithelium of hamsters in vivo. All accumulated data point to β-cyclodextrins as promising broad-spectrum antivirals against different SARS-CoV-2 variants and distant alphacoronaviruses. Given the wide use of β-cyclodextrins for drug encapsulation and their high safety profile in humans, our results support their clinical testing as prophylactic antivirals. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Antiviral | es_ES |
dc.subject | COVID-19 | es_ES |
dc.subject | Coronavirus | es_ES |
dc.subject | Cyclodextrin | es_ES |
dc.subject | Drug repurposing | es_ES |
dc.subject | SARS-CoV-2 | es_ES |
dc.subject | β-cyclodextrin | es_ES |
dc.subject.mesh | COVID-19 | es_ES |
dc.subject.mesh | beta-Cyclodextrins | es_ES |
dc.subject.mesh | Dermatologic Agents | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | SARS-CoV-2 | es_ES |
dc.subject.mesh | Antiviral Agents | es_ES |
dc.title | β-Cyclodextrins as affordable antivirals to treat coronavirus infection | es_ES |
dc.type | research article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 37311279 | es_ES |
dc.format.volume | 164 | es_ES |
dc.format.page | 114997 | es_ES |
dc.identifier.doi | 10.1016/j.biopha.2023.114997 | es_ES |
dc.contributor.funder | Agencia Estatal de Investigación (España) | es_ES |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | es_ES |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (España) | es_ES |
dc.contributor.funder | Fundación Española para la Ciencia y la Tecnología | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. Horizonte Europa | es_ES |
dc.contributor.funder | Grifols (Spain) | es_ES |
dc.contributor.funder | Pharma Mar | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1950-6007 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.biopha.2023.114997 | es_ES |
dc.identifier.journal | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología::Unidades Comunes Científico-Técnicas (UCCT) | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/101046118 | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RTI2018-094445-B100 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2020-117145RB-I00 | es_ES |