2026-04-14T07:32:57Zhttps://recercat.cat/oai/request

oai:recercat.cat:20.500.12327/23812026-03-07T00:31:18Zcom_2072_4428com_2072_4427col_2072_487898

00925njm 22002777a 4500 dc Raïch-Regué, Dalia author Tenorio, Raquel author Fernández de Castro, Isabel author Tarrés Freixas, Ferran author Sachse, Martin author Perez-Zsol, 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 Serra Gironella, Joan 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 2023-06-08 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. 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. 0753-3322 http://hdl.handle.net/20.500.12327/2381 https://doi.org/10.1016/j.biopha.2023.114997 β-Cyclodextrins as affordable antivirals to treat coronavirus infection