PT  - JOURNAL ARTICLE
AU  - Jean-Sélim Driouich
AU  - Maxime Cochin
AU  - Franck Touret
AU  - Paul-Rémi Petit
AU  - Magali Gilles
AU  - Grégory Moureau
AU  - Karine Barthélémy
AU  - Caroline Laprie
AU  - Thanaporn Wattanakul
AU  - Palang Chotsiri
AU  - Richard M. Hoglund
AU  - Joel Tarning
AU  - Fanny Escudié
AU  - Ivan Scandale
AU  - Eric Chatelain
AU  - Xavier de Lamballerie
AU  - Caroline Solas
AU  - Antoine Nougairède
TI  - Pre-clinical evaluation of antiviral activity of nitazoxanide against Sars-CoV-2
AID  - 10.1101/2021.12.17.473113
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.12.17.473113
4099  - http://biorxiv.org/content/early/2021/12/20/2021.12.17.473113.short
4100  - http://biorxiv.org/content/early/2021/12/20/2021.12.17.473113.full
AB  - To address the emergence of SARS-CoV-2, multiple clinical trials in humans were rapidly started, including those involving an oral treatment by nitazoxanide, despite no or limited pre-clinical evidence of antiviral efficacy. In this work, we present a complete pre-clinical evaluation of the antiviral activity of nitazoxanide against SARS-CoV-2. First, we confirmed the in vitro efficacy of nitazoxanide and tizoxanide (its active metabolite) against SARS-CoV-2. Then, we demonstrated nitazoxanide activity in a reconstructed bronchial human airway epithelium model. In a SARS-CoV-2 virus challenge model in hamsters, oral and intranasal treatment with nitazoxanide failed to impair viral replication in commonly affected organs. We hypothesized that this could be due to insufficient diffusion of the drug into organs of interest. Indeed, our pharmacokinetic study confirmed that concentrations of tizoxanide in organs of interest were always below the in vitro EC50. These preclinical results suggest, if directly applicable to humans, that the standard formulation and dosage of nitazoxanide is not effective in providing antiviral therapy for Covid-19.Competing Interest StatementThe authors have declared no competing interest.