2026-04-27T03:42:44Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/168242024-10-17T11:27:46Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Raïch-Regué, Dalia
author
Tenorio, Raquel
author
Fernández de Castro, Isabel
author
Tarrés-Freixas, Ferran
author
Sachse, Martin
author
Perez-Zsolt, Daniel
author
Muñoz-Basagoiti, Jordana
author
Fernández-Sánchez, Sara Y
author
Gallemí, Marçal
author
Ortega-González, Paula
author
Fernández-Oliva, Alberto
author
Gabaldón, José A
author
Nuñez-Delicado, Estrella
author
Casas, Josefina
author
Roca, Núria
author
Cantero, Guillermo
author
Pérez, Mónica
author
Usai, Carla
author
Lorca-Oró, Cristina
author
Alert, Júlia-Vergara
author
Segalés, Joaquim
author
Carrillo, Jorge
author
Blanco, Julià
author
Clotet Sala, Bonaventura
author
Cerón-Carrasco, José P
author
Izquierdo-Useros, Nuria
author
Risco, Cristina
funder
Agencia Estatal de Investigación (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Fundación Española para la Ciencia y la Tecnología
funder
Ministerio de Ciencia e Innovación (España)
funder
Unión Europea. Comisión Europea. Horizonte Europa
funder
Grifols (Spain)
funder
Pharma Mar
2023-12-15T19:47:02Z
2023-12-15T19:47:02Z
2023-08
Biomed Pharmacother. 2023 Aug:164:114997.
http://hdl.handle.net/20.500.12105/16824
37311279
10.1016/j.biopha.2023.114997
1950-6007
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
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.
eng
Antiviral
COVID-19
Coronavirus
Cyclodextrin
Drug repurposing
SARS-CoV-2
β-cyclodextrin
β-Cyclodextrins as affordable antivirals to treat coronavirus infection
research article
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