HPβ-CD as affordable antiviral to treat coronavirus infection

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In a recent study posted to the bioRxiv* preprint server, researchers identified β-cyclodextrins (β-CDs) as a safe and cost-effective drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a broad spectrum of activity.

The team enlisted 116 drugs that have been used previously for treating pathologies or have demonstrated anti-SARS-CoV-2 efficacy in pre-clinical trials. Molecular modeling was performed to rank 44 compounds that showed the greatest efficacy against several α CoVs and β CoVs, e.g., SARS-CoV-2 and
human CoV 229E (HCoV-229E). The drugs were identified by virology, computational chemistry, transmission electron microscopy (TEM), and cell biology techniques.

Four compounds, U18666A, OSW-1, phytol, and hydroxypropyl-β-cyclodextrin (HβCD) demonstrated antiviral activity against HCoV-229E and SARS-CoV-2 in MRC-5 cells and Vero E6 cells, respectively. U18666A and HβCD blocked viral fusion; however, only HβCD showed inhibition of SARS-CoV-2 replication in Calu-3 cells. Testing native and modified cyclodextrins confirmed the potent SARS-CoV-2 inhibition by β-cyclodextrins in Calu-3 cells.

The half maximal inhibitory concentration (IC50) values for U18666A, OSW-1, HβCD, and phytol and were 2.6µM, 0.5nM, 4.3mM, and 19µM, respectively. Cyclodextrins inhibited SARS-CoV-2 replication by interfering with viral fusion via cholesterol depletion. HβCDs, MbCDs, and b-CDs inhibited SARS-CoV-2
D614G strain and BA.1 strain on Calu-3 cells.

HβCD treatment at 0.2 mM concentration altered the inner membrane of DMVs, with large clusters of distorted SARS-CoV-2 particles observed within the vacuoles. At 20 mM HβCD concentration, all structures of SARS-CoV-2 were reduced with few altered DMVs.

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 (2022) β-Cyclodextrins as affordable antivirals to treat coronavirus infection. BioRxiv. doi: https://doi.org/10.1101/2022.11.16.516726

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