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dc.contributor.authorRodon, Jordi
dc.contributor.authorMuñoz-Basagoit, Jordana
dc.contributor.authorPerez-Zsolt, Daniel
dc.contributor.authorNoguera-Julian, Marc
dc.contributor.authorParedes, Roger
dc.contributor.authorMateu, Lourdes
dc.contributor.authorQuiñones, Carles
dc.contributor.authorPerez, Carles
dc.contributor.authorErkizia, Itziar
dc.contributor.authorBlanco, Ignacio
dc.contributor.authorValencia, Alfonso
dc.contributor.authorGuallar, Víctor
dc.contributor.authorCarrillo, Jorge
dc.contributor.authorBlanco, Julià
dc.contributor.authorSegalés, Joaquim
dc.contributor.authorClotet, Bonaventura
dc.contributor.authorVergara-Alert, Júlia
dc.contributor.authorIzquierdo-Useros, Nuria
dc.contributor.otherProducció Animalca
dc.date.accessioned2021-09-22T15:00:22Z
dc.date.available2021-09-22T15:00:22Z
dc.date.issued2021-03-25
dc.identifier.citationRodon, Jordi, Jordana Muñoz-Basagoiti, Daniel Perez-Zsolt, Marc Noguera-Julian, Roger Paredes, Lourdes Mateu, Carles Quiñones, Carles Perez, Itziar Erkizia, Ignacio Blanco, Alfonso Valencia, Víctor Guallar, Jorge Carrillo, Julià Blanco, Joaquim Segalés, Bonaventura Clotet, Júlia Vergara-Alert, Nuria Izquierdo-Useros. 2021. "Identification Of Plitidepsin As Potent Inhibitor Of SARS-Cov-2-Induced Cytopathic Effect After A Drug Repurposing Screen". Frontiers In Pharmacology 12. doi:10.3389/fphar.2021.646676.ca
dc.identifier.issn1663-9812ca
dc.identifier.urihttp://hdl.handle.net/20.500.12327/1342
dc.description.abstractThere is an urgent need to identify therapeutics for the treatment of Coronavirus disease 2019 (COVID-19). Although different antivirals are given for the clinical management of SARS-CoV-2 infection, their efficacy is still under evaluation. Here, we have screened existing drugs approved for human use in a variety of diseases, to compare how they counteract SARS-CoV-2-induced cytopathic effect and viral replication in vitro. Among the potential 72 antivirals tested herein that were previously proposed to inhibit SARS-CoV-2 infection, only 18 % had an IC50 below 25 µM or 102 IU/ml. These included plitidepsin, novel cathepsin inhibitors, nelfinavir mesylate hydrate, interferon 2-alpha, interferon-gamma, fenofibrate, camostat along the well-known remdesivir and chloroquine derivatives. Plitidepsin was the only clinically approved drug displaying nanomolar efficacy. Four of these families, including novel cathepsin inhibitors, blocked viral entry in a cell-type specific manner. Since the most effective antivirals usually combine therapies that tackle the virus at different steps of infection, we also assessed several drug combinations. Although no particular synergy was found, inhibitory combinations did not reduce their antiviral activity. Thus, these combinations could decrease the potential emergence of resistant viruses. Antivirals prioritized herein identify novel compounds and their mode of action, while independently replicating the activity of a reduced proportion of drugs which are mostly approved for clinical use. Combinations of these drugs should be tested in animal models to inform the design of fast track clinical trials.ca
dc.format.extent12ca
dc.language.isoengca
dc.publisherFrontiers Mediaca
dc.relation.ispartofFrontiers in Pharmacologyca
dc.rightsAttribution 4.0 Internationalca
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleIdentification of Plitidepsin as Potent Inhibitor of SARS-CoV-2-Induced Cytopathic Effect After a Drug Repurposing Screenca
dc.typeinfo:eu-repo/semantics/articleca
dc.description.versioninfo:eu-repo/semantics/publishedVersionca
dc.rights.accessLevelinfo:eu-repo/semantics/openAccess
dc.embargo.termscapca
dc.subject.udc619ca
dc.identifier.doihttps://doi.org/10.3389/fphar.2021.646676ca
dc.contributor.groupSanitat Animalca


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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/