2026-04-27T03:42:38Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/168242024-10-17T11:27:46Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Raïch-Regué, Dalia author Tenorio, Raquel author Fernández de Castro, Isabel author Tarrés-Freixas, Ferran author Sachse, Martin author Perez-Zsolt, Daniel author Muñoz-Basagoiti, Jordana author Fernández-Sánchez, Sara Y author Gallemí, Marçal author Ortega-González, Paula author Fernández-Oliva, Alberto author Gabaldón, José A author Nuñez-Delicado, Estrella author Casas, Josefina author Roca, Núria author Cantero, Guillermo author Pérez, Mónica author Usai, Carla author Lorca-Oró, Cristina author Alert, Júlia-Vergara author Segalés, Joaquim author Carrillo, Jorge author Blanco, Julià author Clotet Sala, Bonaventura author Cerón-Carrasco, José P author Izquierdo-Useros, Nuria author Risco, Cristina author 2023-08 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. Biomed Pharmacother. 2023 Aug:164:114997. http://hdl.handle.net/20.500.12105/16824 37311279 10.1016/j.biopha.2023.114997 1950-6007 Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Antiviral COVID-19 Coronavirus Cyclodextrin Drug repurposing SARS-CoV-2 β-cyclodextrin β-Cyclodextrins as affordable antivirals to treat coronavirus infection