Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/16824
Title
β-Cyclodextrins as affordable antivirals to treat coronavirus infection
Author(s)
Raïch-Regué, Dalia | Tenorio, Raquel | Fernández de Castro, Isabel | Tarrés-Freixas, Ferran | Sachse, Martin ISCIII | 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
Date issued
2023-08
Citation
Biomed Pharmacother. 2023 Aug:164:114997.
Language
Inglés
Document type
research article
Abstract
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.
Subject
MESH
Online version
DOI
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