β-Cyclodextrins as affordable antivirals to treat coronavirus infection
Author/s
Raïch Regué, Dalia; Tenorio, Raquel; Fernández de Castro, Isabel; Tarrés Freixas, Ferrán; Sachse, Martín; [et al.]Date
2023-06-06Discipline/s
FarmaciaMedicina
Subject/s
SARS-CoV-2COVID-19
Coronavirus
Antiviral
Drug repurposing
Cyclodextrin
β-cyclodextrin
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 ...