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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| 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 |
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β-Cyclodextrins as affordable antivirals to treat coronavirus infectionRaïch Regué, DaliaTenorio, RaquelFernández de Castro, IsabelTarrés Freixas, FerránSachse, MartínPerez Zsolt, DanielMuñoz Basagoiti, JordanaFernández Sánchez, Sara YGallemí, MarçalFernández Oliva, AlbertoGabaldón, José AntonioCasas, JosefinaRoca, NuriaCantero, GuillermoPérez, MónicaUsai, CarlaLorca Oró, CristinaVergara Alert, JuliaSegalés, JoaquimCarrillo, JorgeBlanco, JuliaBonaventura Clotet, SalaCerón Carrasco, José PedroIzquierdo Useros, NuriaRisco, CristinaOrtega González, PaulaNúñez Delicado, EstrellaSARS-CoV-2COVID-19CoronavirusAntiviralDrug repurposingCyclodextrinβ-cyclodextrinThe 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.FarmaciaMedicina2023info:eu-repo/semantics/articlehttp://hdl.handle.net/10952/7958reponame:RIUCAM. Repositorio Institucional de la Universidad Católica San Antonio de Murciainstname:Universidad Católica San Antonio de Murcia (UCAM)InglésPID2020-117145RB-I00, RTI2018-094445-B100, EU HORIZON-HLTH-2021-CORONA-01 (grant 101046118)info:eu-repo/semantics/openAccessoai:repositorio.ucam.edu:10952/79582026-06-07T18:35:21Z |
| dc.title.none.fl_str_mv |
β-Cyclodextrins as affordable antivirals to treat coronavirus infection |
| title |
β-Cyclodextrins as affordable antivirals to treat coronavirus infection |
| spellingShingle |
β-Cyclodextrins as affordable antivirals to treat coronavirus infection Raïch Regué, Dalia SARS-CoV-2 COVID-19 Coronavirus Antiviral Drug repurposing Cyclodextrin β-cyclodextrin |
| title_short |
β-Cyclodextrins as affordable antivirals to treat coronavirus infection |
| title_full |
β-Cyclodextrins as affordable antivirals to treat coronavirus infection |
| title_fullStr |
β-Cyclodextrins as affordable antivirals to treat coronavirus infection |
| title_full_unstemmed |
β-Cyclodextrins as affordable antivirals to treat coronavirus infection |
| title_sort |
β-Cyclodextrins as affordable antivirals to treat coronavirus infection |
| dc.creator.none.fl_str_mv |
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 |
| author |
Raïch Regué, Dalia |
| author_facet |
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 |
| author_role |
author |
| author2 |
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 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
SARS-CoV-2 COVID-19 Coronavirus Antiviral Drug repurposing Cyclodextrin β-cyclodextrin |
| topic |
SARS-CoV-2 COVID-19 Coronavirus Antiviral Drug repurposing Cyclodextrin β-cyclodextrin |
| description |
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. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10952/7958 |
| url |
http://hdl.handle.net/10952/7958 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
PID2020-117145RB-I00, RTI2018-094445-B100, EU HORIZON-HLTH-2021-CORONA-01 (grant 101046118) |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.source.none.fl_str_mv |
reponame:RIUCAM. Repositorio Institucional de la Universidad Católica San Antonio de Murcia instname:Universidad Católica San Antonio de Murcia (UCAM) |
| instname_str |
Universidad Católica San Antonio de Murcia (UCAM) |
| reponame_str |
RIUCAM. Repositorio Institucional de la Universidad Católica San Antonio de Murcia |
| collection |
RIUCAM. Repositorio Institucional de la Universidad Católica San Antonio de Murcia |
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|
| repository.mail.fl_str_mv |
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1869422787153625088 |
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15,812429 |