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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Detalhes bibliográficos
Autores: Raïch-Regué, Dàlia|||0000-0001-7656-5700, Tenorio, Raquel, Fernández de Castro, Isabel, Tarrés-Freixas, Ferran|||0000-0002-1569-0126, Sachse, Martin, Perez-Zsolt, Daniel|||0000-0003-4192-7622, Muñoz-Basagoiti, Jordana|||0000-0002-0384-5928, Fernández-Sánchez, Sara Y., Gallemí, Marçal|||0000-0003-4675-6893, Ortega-González, Paula, Fernández-Oliva, Alberto, Gabaldón, José A., Nuñez-Delicado, Estrella, Casas, Josefina|||0000-0002-7926-5209, Roca, Núria, Cantero, Guillermo|||0000-0003-4200-503X, Pérez, Mónica, Usai, Carla|||0000-0002-6373-2765, Lorca-Oró, Cristina|||0000-0001-5351-4169, Vergara-Alert, Júlia|||0000-0001-7484-444X, Segalés Coma, Joaquim|||0000-0002-1539-7261, Carrillo, Jorge|||0000-0003-0221-5948, Blanco, Julià|||0000-0002-2225-0217, Clotet Sala, Bonaventura|||0000-0003-3232-4598, Cerón-Carrasco, José P., Izquierdo Useros, Nuria|||0000-0002-1039-1821, Risco, Cristina|||0000-0001-7501-5934
Formato: artículo
Fecha de publicación:2023
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:275883
Acesso em linha:https://ddd.uab.cat/record/275883
https://dx.doi.org/urn:doi:10.1016/j.biopha.2023.114997
Access Level:acceso abierto
Palavra-chave:SARS-CoV-2
COVID-19
Coronavirus
Antiviral
Drug repurposing
Cyclodextrin
Β-cyclodextrin
Descrição
Resumo: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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