β-Cyclodextrins as affordable antivirals to treat coronavirus infection.
|
| 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.
|
|---|---|
| Authors | Dalia Raïch-Regué, Raquel Tenorio, Isabel Fernández de Castro, Ferran Tarrés-Freixas, Martin Sachse, Daniel Perez-Zsolt, Jordana Muñoz-Basagoiti, Sara Y Fernández-Sánchez, Marçal Gallemí, Paula Ortega-González, Alberto Fernández-Oliva, José A Gabaldón, Estrella Nuñez-Delicado, Josefina Casas, Núria Roca, Guillermo Cantero, Mónica Pérez, Carla Usai, Cristina Lorca-Oró, Júlia-Vergara Alert, Joaquim Segalés, Jorge Carrillo, Julià Blanco, Bonaventura Clotet Sala, José P Cerón-Carrasco, Nuria Izquierdo-Useros, Cristina Risco |
| Journal | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 164 Pg. 114997 (Aug 2023) ISSN: 1950-6007 [Electronic] France |
| PMID | 37311279 (Publication Type: Journal Article) |
| Copyright | Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!