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, Dalia, Tenorio, Raquel, Fernández de Castro, Isabel, Tarrés Freixas, Ferrán, Sachse, Martín, Perez Zsolt, Daniel, Muñoz Basagoiti, Jordana, Fernández Sánchez, Sara Y, Gallemí, Marçal, Fernández Oliva, Alberto, Gabaldón, José Antonio, Casas, Josefina, Roca, Nuria, Cantero, Guillermo, Pérez, Mónica, Usai, Carla, Lorca Oró, Cristina, Vergara Alert, Julia, Segalés, Joaquim, Carrillo, Jorge, Blanco, Julia, Bonaventura Clotet, Sala, Cerón Carrasco, José Pedro, Izquierdo Useros, Nuria, Risco, Cristina, Ortega González, Paula, Núñez Delicado, Estrella
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Católica San Antonio de Murcia (UCAM)
Repositorio:RIUCAM. Repositorio Institucional de la Universidad Católica San Antonio de Murcia
OAI Identifier:oai:repositorio.ucam.edu:10952/7958
Acceso en línea:http://hdl.handle.net/10952/7958
Access Level:acceso abierto
Palabra clave:SARS-CoV-2
COVID-19
Coronavirus
Antiviral
Drug repurposing
Cyclodextrin
β-cyclodextrin
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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