β-Cyclodextrins as affordable antivirals to treat coronavirus infection.

Autor: Raïch-Regué D; IrsiCaixa, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, 08916, Badalona, Spain., Tenorio R; Cell Structure Lab, Centro Nacional de Biotecnologia, CNB - CSIC, Campus de Cantoblanco, 28049 Madrid, Spain., Fernández de Castro I; Cell Structure Lab, Centro Nacional de Biotecnologia, CNB - CSIC, Campus de Cantoblanco, 28049 Madrid, Spain., Tarrés-Freixas F; IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la UAB, 08193 Bellaterra (Cerdanyola del Vallès), Spain; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, Spain., Sachse M; Cell Structure Lab, Centro Nacional de Biotecnologia, CNB - CSIC, Campus de Cantoblanco, 28049 Madrid, Spain., Perez-Zsolt D; IrsiCaixa, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, 08916, Badalona, Spain., Muñoz-Basagoiti J; IrsiCaixa, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, 08916, Badalona, Spain., Fernández-Sánchez SY; Cell Structure Lab, Centro Nacional de Biotecnologia, CNB - CSIC, Campus de Cantoblanco, 28049 Madrid, Spain., Gallemí M; IrsiCaixa, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, 08916, Badalona, Spain., Ortega-González P; Cell Structure Lab, Centro Nacional de Biotecnologia, CNB - CSIC, Campus de Cantoblanco, 28049 Madrid, Spain., Fernández-Oliva A; Cell Structure Lab, Centro Nacional de Biotecnologia, CNB - CSIC, Campus de Cantoblanco, 28049 Madrid, Spain., Gabaldón JA; Reconocimiento y Encapsulación Molecular. Universidad Católica San Antonio de Murcia (UCAM), Campus de los Jerónimos, N° 135, Guadalupe, 30107 Murcia, Spain., Nuñez-Delicado E; Reconocimiento y Encapsulación Molecular. Universidad Católica San Antonio de Murcia (UCAM), Campus de los Jerónimos, N° 135, Guadalupe, 30107 Murcia, Spain., Casas J; Institut de Química Avançada de Catalunya (IQAC-CSIC), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, 28029 Madrid, Spain., Roca N; IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la UAB, 08193 Bellaterra (Cerdanyola del Vallès), Spain; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, Spain., Cantero G; IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la UAB, 08193 Bellaterra (Cerdanyola del Vallès), Spain; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, Spain., Pérez M; IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la UAB, 08193 Bellaterra (Cerdanyola del Vallès), Spain; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, Spain., Usai C; IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la UAB, 08193 Bellaterra (Cerdanyola del Vallès), Spain; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, Spain., Lorca-Oró C; IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la UAB, 08193 Bellaterra (Cerdanyola del Vallès), Spain; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, Spain., Alert JV; IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la UAB, 08193 Bellaterra (Cerdanyola del Vallès), Spain; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, Spain., Segalés J; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, Spain; Departament de Sanitat i Anatomia Animals, Facultat de Veterinària, UAB, 08193 Bellaterra (Cerdanyola del Vallès), Spain., Carrillo J; IrsiCaixa, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, 08916, Badalona, Spain., Blanco J; IrsiCaixa, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, 08916, Badalona, Spain; University of Vic-Central University of Catalonia (UVic-UCC), 08500 Vic, Spain; Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain., Clotet Sala B; IrsiCaixa, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, 08916, Badalona, Spain; University of Vic-Central University of Catalonia (UVic-UCC), 08500 Vic, Spain; Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain., Cerón-Carrasco JP; Centro Universitario de la Defensa, Universidad Politécnica de Cartagena, C/Coronel López Peña s/n, Base Aérea de San Javier, Santiago de la Ribera, 30720 Murcia, Spain. Electronic address: jose.ceron@cud.upct.es., Izquierdo-Useros N; IrsiCaixa, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, 08916, Badalona, Spain; Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain. Electronic address: nizquierdo@irsicaixa.es., Risco C; Cell Structure Lab, Centro Nacional de Biotecnologia, CNB - CSIC, Campus de Cantoblanco, 28049 Madrid, Spain. Electronic address: crisco@cnb.csic.es.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2023 Aug; Vol. 164, pp. 114997. Date of Electronic Publication: 2023 Jun 08.
DOI: 10.1016/j.biopha.2023.114997
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CR, IFC, MS, RT, PO-G, AF-O, SF-S, NI-U, DP-Z, JM-B, DR-R, JPC-C, JAG and EN-D are inventors of a patent application for use of cyclodextrins to treat viral infection (PCT/EP2023/057735). The authors declare no other related competing interest.
(Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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