β-Cyclodextrins as affordable antivirals to treat coronavirus infection
| Autor: | Dalia Raïch-Regué, Raquel Tenorio, Isabel Fernández de Castro, Daniel Perez -Zsolt, Jordana Muñoz-Basagoiti, Martin Sachse, Sara Y. Fernández-Sánchez, Marçal Gallemí, Paula Ortega-González, Alberto Fernández-Oliva, José A. Gabaldón, Estrella Nuñez-Delicado, Josefina Casas, Ferran Tarrés, Júlia-Vergara Alert, Joaquim Segalés, Jorge Carillo, Julià Blanco, Bonaventura Clotet Sala, José P. Cerón-Carrasco, Nuria Izquierdo-Useros, Cristina Risco |
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| Přispěvatelé: | Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Fundación Española para la Ciencia y la Tecnología, Grifols, PharmaMar, Hipra, Amassence, Palobiofarma, Palex Medical, SIKA, Izquierdo-Useros, Núria, Risco, Cristina |
| Rok vydání: | 2022 |
| Předmět: | |
| Popis: | The SARS-CoV-2 pandemic made evident that we count with few coronavirus-fighting drugs. Here we aimed to identify a cost-effective antiviral with broad spectrum activity and high safety and tolerability profiles. We began elaborating a list of 116 drugs previously used to treat other pathologies or characterized in pre-clinical studies with potential to treat coronavirus infections. We next employed molecular modelling tools to rank the 44 most promising inhibitors and tested their efficacy as antivirals against a panel of alpha and beta coronavirus, e.g., the HCoV-229E and SARS-CoV-2 viruses. Four drugs, OSW-1, U18666A, hydroxypropyl-beta-cyclodextrin (HbetaCD) and phytol, showed antiviral activity against both HCoV-229E (in MRC5 cells) and SARS-CoV-2 (in Vero E6 cells). The mechanism of action of these compounds was studied by transmission electron microscopy (TEM) and by testing their capacity to inhibit the entry of SARS-CoV-2 pseudoviruses in ACE2-expressing HEK-293T cells. The entry was inhibited by HbetaCD and U18666A, yet only HbetaCD could inhibit SARS-CoV-2 replication in the pulmonary cells Calu-3. With these results and given that cyclodextrins are widely used for drug encapsulation and can be safely administered to humans, we further tested 6 native and modified cyclodextrins, which confirmed β-cyclodextrins as the most potent inhibitors of SARS-CoV-2 replication in Calu-3 cells. All accumulated data points to beta-cyclodextrins as promising candidates to be used in the therapeutic treatments for SARS-CoV-2 and possibly other respiratory viruses. This work has been funded by grant RTI2018-094445-B100 (MCIU/AEI/FEDER, UE) from the Ministry of Science and Innovation of Spain (C.R.), by Palex Medical S.A., Sika S.A.U. and 7 more companies, and by Ms. Raquel Casaus Alvarez, Mr. Miguel Pardo Gil, Mr. Jacques Noguès and a total of 2,916 citizens through the Precipita crowdfunding platform of Fecyt (Fundación Española para la Ciencia y la Tecnología). NI-U is supported by the Spanish Ministry of Science and Innovation (grant PID2020-117145RB-I00), EU HORIZON-HLTH-2021-CORONA-01 (grant 101046118) and by institutional funding of Grifols, Pharma Mar, HIPRA, Amassence and Palobiofarma. This work used the computational resources of the Centro de Supercomputación de Galicia (CESGA) supported by the Partnership for Advanced Computing in Europe (PRACE) COVID-19 Fast Track Call for Proposals – Allocation Decision – Proposal COVID19-85. |
| Databáze: | OpenAIRE |
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