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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Detalles Bibliográficos
Autores: Raïch-Regué, Dàlia, Tenorio, Raquel, Fernández de Castro, Isabel, Tarrés-Freixas, Ferran, Sachse, Martín, Perez-Zsolt, Daniel, Muñoz-Basagoiti, Jordana, Fernández-Sánchez, Sara Yolanda, Gallemí, Marçal, Ortega-González, Paula, Fernández-Oliva, Alberto, Gabaldón, José A., Núñez-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, Núria, Risco, Cristina
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/329462
Acceso en línea:http://hdl.handle.net/10261/329462
https://api.elsevier.com/content/abstract/scopus_id/85161350853
Access Level:acceso abierto
Palabra clave:β-cyclodextrin
Antiviral
COVID-19
Coronavirus
Cyclodextrin
Drug repurposing
SARS-CoV-2
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
Descripción
Sumario: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.

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