In vitro activity of itraconazole against SARS-CoV-2

  • Although vaccination campaigns are currently being rolled out to prevent coronavirus disease (COVID-19), antivirals will remain an important adjunct to vaccination. Antivirals against coronaviruses do not exist, hence global drug repurposing efforts have been carried out to identify agents that may provide clinical benefit to patients with COVID-19. Itraconazole, an antifungal agent, has been reported to have activity against animal coronaviruses. Using cell-based phenotypic assays, the in vitro antiviral activity of itraconazole and 17-OH itraconazole was assessed against clinical isolates from a German and Belgian patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Itraconazole demonstrated antiviral activity in human Caco-2 cells (EC50 = 2.3 µM; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay). Similarly, its primary metabolite, 17-OH itraconazole, showed inhibition of SARS-CoV-2 activity (EC50 = 3.6 µM). Remdesivir inhibited viral replication with an EC50 = 0.4 µM. Itraconazole and 17-OH itraconazole resulted in a viral yield reduction in vitro of approximately 2-log10 and approximately 1-log10, as measured in both Caco-2 cells and VeroE6-eGFP cells, respectively. The viral yield reduction brought about by remdesivir or GS-441524 (parent nucleoside of the antiviral prodrug remdesivir; positive control) was more pronounced, with an approximately 3-log10 drop and >4-log10 drop in Caco-2 cells and VeroE6-eGFP cells, respectively. Itraconazole and 17-OH itraconazole exert in vitro low micromolar activity against SARS-CoV-2. Despite the in vitro antiviral activity, itraconazole did not result in a beneficial effect in hospitalized COVID-19 patients in a clinical study (EudraCT Number: 2020-001243-15).

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Author:Ellen van DammeORCiD, Sandra De MeyerORCiD, Denisa BojkovaORCiDGND, Sandra CiesekORCiDGND, Jindrich CinatlORCiDGND, Steven De JongheORCiD, Dirk JochmansORCiDGND, Pieter LeyssenORCiD, Christophe BuyckORCiD, Johan NeytsORCiD, Marnix van LoockORCiD
Parent Title (English):Journal of medical virology
Place of publication:Bognor Regis [u.a.]
Document Type:Article
Date of Publication (online):2021/03/05
Date of first Publication:2021/03/05
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/02/17
Tag:17‐OH itraconazole; Caco‐2 cells; SARS‐CoV‐2; VeroE6‐eGFP cells; in vitro; itraconazole
Page Number:8
First Page:4454
Last Page:4460
This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement no.: 101003627. Part of this study work was performed using the “Caps-It” research infrastructure (project ZW13-02) that was financially supported by the Hercules Foundation and Rega Foundation, KU, Leuven. This study has been funded in part with Federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under OTA No. HHSO100201800012C. Medical writing support for the development of this manuscript was provided by Patrick Hoggard of Zoetic Science, an Ashfield company, part of UDG Healthcare plc; this support was funded by Janssen Pharmaceuticals.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0