β-Cyclodextrins as affordable antivirals to treat coronavirus infection
Author
Raïch-Regué, Dalia
Tenorio, Raquel
Fernández de Castro, Isabel
Sachse, Martin
Perez-Zsol, 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
Pérez, Mónica
Lorca-Oró, Cristina
Vergara-Alert, Júlia
Carrillo, Jorge
Blanco, Julià
Clotet Sala, Bonaventura
Cerón-Carrasco, José P.
Izquierdo-Useros, Nuria
Risco, Cristina
Publication date
2023-06-08ISSN
0753-3322
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.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
619 - Veterinary science
Pages
18
Publisher
Elsevier
Is part of
Biomedicine and Pharmacotherapy
Citation
Raïch‐Regué, Dàlia, Raquel Tenorio, Castro Isabel Fernández De, Ferran Tarrés-Freixas, Martin Sachse, Daniel Perez-Zsolt, Jordana Muñoz-Basagoiti, et al. 2023. “β-Cyclodextrins as Affordable Antivirals to Treat Coronavirus Infection.” Biomedicine & Pharmacotherapy 164 (August): 114997. doi:10.1016/j.biopha.2023.114997.
Grant agreement number
MICIU/Programa Estatal de I+D+I orientada a los retos de la sociedad/RTI2018-094445-B-I00/ES/BUSQUEDA DE NUEVOS ANTIVIRALES DE AMPLIO ESPECTRO: TRANSPORTE DE LIPIDOS Y PROTEINAS MITOCONDRIALES COMO DIANAS/
MICINN/Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2020-117145RB-I00/ES/NUEVAS TERAPIAS ANTIVIRALES E INMUNOMODULADORAS FRENTE AL SARS-COV-2/
EU/H2020/101046118/EC/RBD Dimer recombinant protein vaccine against SARSCoV2/RBDCOV
FEDER/ / /EU/ /
Program
Sanitat Animal
This item appears in the following Collection(s)
- ARTICLES CIENTÍFICS [2635]
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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-nd/4.0/