β-Cyclodextrins as affordable antivirals to treat coronavirus infection

Raïch-Regué, Dalia; Tenorio, Raquel; Fernández de Castro, Isabel; Tarrés-Freixas, Ferran; Sachse, Martin; Perez-Zsolt, Daniel; Muñoz-Basagoiti, Jordana; Fernández-Sánchez, Sara Y; Gallemí, Marçal; Ortega-González, Paula; Fernández-Oliva, Alberto; Gabaldón, José A; Nuñez-Delicado, Estrella; Casas, Josefina; Roca, Núria; Cantero, Guillermo; Pérez, Mónica; Usai, Carla; Lorca-Oró, Cristina; Alert, Júlia-Vergara; Segalés, Joaquim; Carrillo, Jorge; Blanco, Julià; Clotet Sala, Bonaventura; Cerón-Carrasco, José P; Izquierdo-Useros, Nuria; Risco, Cristina

β-Cyclodextrins as affordable antivirals to treat coronavirus infection

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 prom...

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Authors:	Raïch-Regué, Dalia, Tenorio, Raquel, Fernández de Castro, Isabel, Tarrés-Freixas, Ferran, Sachse, Martin, Perez-Zsolt, Daniel, Muñoz-Basagoiti, Jordana, Fernández-Sánchez, Sara Y, Gallemí, Marçal, Ortega-González, Paula, Fernández-Oliva, Alberto, Gabaldón, José A, Nuñez-Delicado, Estrella, Casas, Josefina, Roca, Núria, Cantero, Guillermo, Pérez, Mónica, Usai, Carla, Lorca-Oró, Cristina, Alert, Júlia-Vergara, Segalés, Joaquim, Carrillo, Jorge, Blanco, Julià, Clotet Sala, Bonaventura, Cerón-Carrasco, José P, Izquierdo-Useros, Nuria, Risco, Cristina
Format:	article
Publication Date:	2023
Country:	España
Institution:	Instituto de Salud Carlos III (ISCIII)
Repository:	Repisalud
Language:	English
OAI Identifier:	oai:repisalud.isciii.es:20.500.12105/16824
Online Access:	http://hdl.handle.net/20.500.12105/16824
Access Level:	Open access
Keyword:	COVID-19 beta-Cyclodextrins Dermatologic Agents Humans SARS-CoV-2 Antiviral Agents

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spelling	β-Cyclodextrins as affordable antivirals to treat coronavirus infectionRaïch-Regué, DaliaTenorio, RaquelFernández de Castro, IsabelTarrés-Freixas, FerranSachse, MartinPerez-Zsolt, DanielMuñoz-Basagoiti, JordanaFernández-Sánchez, Sara YGallemí, MarçalOrtega-González, PaulaFernández-Oliva, AlbertoGabaldón, José ANuñez-Delicado, EstrellaCasas, JosefinaRoca, NúriaCantero, GuillermoPérez, MónicaUsai, CarlaLorca-Oró, CristinaAlert, Júlia-VergaraSegalés, JoaquimCarrillo, JorgeBlanco, JuliàClotet Sala, BonaventuraCerón-Carrasco, José PIzquierdo-Useros, NuriaRisco, CristinaCOVID-19beta-CyclodextrinsDermatologic AgentsHumansSARS-CoV-2Antiviral AgentsThe 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.ElsevierAgencia Estatal de Investigación (España)Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Ministerio de Ciencia, Innovación y Universidades (España)Fundación Española para la Ciencia y la TecnologíaMinisterio de Ciencia e Innovación (España)Unión Europea. Comisión Europea. Horizonte EuropaGrifols (Spain)Pharma Mar20232023-12-1520232023-08-0120232023-08-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfimage/jpegimage/jpegimage/jpegimage/jpegimage/jpegimage/jpegimage/jpegimage/jpegimage/jpegimage/jpeghttp://hdl.handle.net/20.500.12105/16824reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengEC 101046118 Not availableopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/168242026-06-12T12:43:37Z
dc.title.none.fl_str_mv	β-Cyclodextrins as affordable antivirals to treat coronavirus infection
title	β-Cyclodextrins as affordable antivirals to treat coronavirus infection
spellingShingle	β-Cyclodextrins as affordable antivirals to treat coronavirus infection Raïch-Regué, Dalia COVID-19 beta-Cyclodextrins Dermatologic Agents Humans SARS-CoV-2 Antiviral Agents
title_short	β-Cyclodextrins as affordable antivirals to treat coronavirus infection
title_full	β-Cyclodextrins as affordable antivirals to treat coronavirus infection
title_fullStr	β-Cyclodextrins as affordable antivirals to treat coronavirus infection
title_full_unstemmed	β-Cyclodextrins as affordable antivirals to treat coronavirus infection
title_sort	β-Cyclodextrins as affordable antivirals to treat coronavirus infection
dc.creator.none.fl_str_mv	Raïch-Regué, Dalia Tenorio, Raquel Fernández de Castro, Isabel Tarrés-Freixas, Ferran Sachse, Martin Perez-Zsolt, Daniel Muñoz-Basagoiti, Jordana Fernández-Sánchez, Sara Y Gallemí, Marçal Ortega-González, Paula Fernández-Oliva, Alberto Gabaldón, José A Nuñez-Delicado, Estrella Casas, Josefina Roca, Núria Cantero, Guillermo Pérez, Mónica Usai, Carla Lorca-Oró, Cristina Alert, Júlia-Vergara Segalés, Joaquim Carrillo, Jorge Blanco, Julià Clotet Sala, Bonaventura Cerón-Carrasco, José P Izquierdo-Useros, Nuria Risco, Cristina
author	Raïch-Regué, Dalia
author_facet	Raïch-Regué, Dalia Tenorio, Raquel Fernández de Castro, Isabel Tarrés-Freixas, Ferran Sachse, Martin Perez-Zsolt, Daniel Muñoz-Basagoiti, Jordana Fernández-Sánchez, Sara Y Gallemí, Marçal Ortega-González, Paula Fernández-Oliva, Alberto Gabaldón, José A Nuñez-Delicado, Estrella Casas, Josefina Roca, Núria Cantero, Guillermo Pérez, Mónica Usai, Carla Lorca-Oró, Cristina Alert, Júlia-Vergara Segalés, Joaquim Carrillo, Jorge Blanco, Julià Clotet Sala, Bonaventura Cerón-Carrasco, José P Izquierdo-Useros, Nuria Risco, Cristina
author_role	author
author2	Tenorio, Raquel Fernández de Castro, Isabel Tarrés-Freixas, Ferran Sachse, Martin Perez-Zsolt, Daniel Muñoz-Basagoiti, Jordana Fernández-Sánchez, Sara Y Gallemí, Marçal Ortega-González, Paula Fernández-Oliva, Alberto Gabaldón, José A Nuñez-Delicado, Estrella Casas, Josefina Roca, Núria Cantero, Guillermo Pérez, Mónica Usai, Carla Lorca-Oró, Cristina Alert, Júlia-Vergara Segalés, Joaquim Carrillo, Jorge Blanco, Julià Clotet Sala, Bonaventura Cerón-Carrasco, José P Izquierdo-Useros, Nuria Risco, Cristina
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Agencia Estatal de Investigación (España) Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) Ministerio de Ciencia, Innovación y Universidades (España) Fundación Española para la Ciencia y la Tecnología Ministerio de Ciencia e Innovación (España) Unión Europea. Comisión Europea. Horizonte Europa Grifols (Spain) Pharma Mar
dc.subject.none.fl_str_mv	COVID-19 beta-Cyclodextrins Dermatologic Agents Humans SARS-CoV-2 Antiviral Agents
topic	COVID-19 beta-Cyclodextrins Dermatologic Agents Humans SARS-CoV-2 Antiviral Agents
description	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.
publishDate	2023
dc.date.none.fl_str_mv	2023 2023-12-15 2023 2023-08-01 2023 2023-08-01
dc.type.none.fl_str_mv	research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	http://hdl.handle.net/20.500.12105/16824
url	http://hdl.handle.net/20.500.12105/16824
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.relation.none.fl_str_mv	EC 101046118 Not available
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf image/jpeg image/jpeg image/jpeg image/jpeg image/jpeg image/jpeg image/jpeg image/jpeg image/jpeg image/jpeg
dc.publisher.none.fl_str_mv	Elsevier
publisher.none.fl_str_mv	Elsevier
dc.source.none.fl_str_mv	reponame:Repisalud instname:Instituto de Salud Carlos III (ISCIII)
instname_str	Instituto de Salud Carlos III (ISCIII)
reponame_str	Repisalud
collection	Repisalud
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repository.mail.fl_str_mv
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β-Cyclodextrins as affordable antivirals to treat coronavirus infection

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