Itraconazole for COVID-19: Preclinical Studies and a Proof-of-Concept Pilot Clinical Study

Liesenborghs, Laurens; Spriet, Isabel; Jochmans, Dirk; Belmans, Ann; Gyselinck, Iwein; Teuwen, Laure-Anne; St, Horst; Dreesen, Erwin; Geukens, Tatjana; Engelen, Matthias M; Landeloos, Ewout; Geldhof,; Debaveye, Barbara; Vandenberk, Bert; LVd, Linden; Jacobs, Sofie; Langendries, Lana; Boudewijns, Robbert; Weynand, Birgit; Vanassche, Thomas; Devos, Timothy; Meyfroidt, Geert; Janssens, Wim; Vos, Robin; Vermeersch, Pieter; Wauters, Joost; Verbeke, Geert; Pd, Munter; Kaptein, Suzanne; Jd, Rocha-Pereira; Ev, Wijngaerden; Neyts, Johan; Verhamme, Peter

doi:10.2139/ssrn.3731461

Cited by 1 publication

(2 citation statements)

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“…Based on these in vitro findings, a clinical study in hospitalized COVID‐19 patients was initiated by UZ Leuven in March 2020 37 . This clinical study was ended prematurely because of futility 38 . Other studies in nonhospitalized patients have not been conducted.…”

Section: Discussionmentioning

confidence: 99%

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In vitro activity of itraconazole against SARS‐CoV‐2

Damme

Meyer

Bojkova

et al. 2021

Journal of Medical Virology

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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 SARS‐CoV‐2. Itraconazole demonstrated antiviral activity in human Caco‐2 cells (EC 50 = 2.3 µM; MTT assay). Similarly, its primary metabolite, 17‐OH itraconazole, showed inhibition of SARS‐CoV‐2 activity (EC 50 = 3.6 µM). Remdesivir inhibited viral replication with an EC 50 = 0.4 µM. Itraconazole and 17‐OH itraconazole resulted in a viral yield reduction in vitro of approximately 2‐log 10 and approximately 1‐log 10 , 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‐log 10 drop and >4‐log 10 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). This article is protected by copyright. All rights reserved.

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Section: Discussionmentioning

confidence: 99%

“…37 This clinical study was ended prematurely because of futility. 38 Other studies in nonhospitalized patients have not been conducted.…”

Section: In Vitro Vrna Yield Reductionmentioning

confidence: 99%