Pre-clinical evaluation of antiviral activity of nitazoxanide against SARS-CoV-2

Journal article

Background
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.

Methods
In this work, we present a complete pre-clinical evaluation of the antiviral activity of nitazoxanide against SARS-CoV-2.

Findings
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.

Interpretation
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.

Authors: Driouich, J-S; Cochin, M; Touret, F; Petit, P-R; Gilles, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: EBioMedicine
• Volume: 82
• Article number: 104148
• Publication date: 2022-07-10
• Acceptance date: 2022-06-22
• DOI: 10.1016/j.ebiom.2022.104148
• EISSN: 2352-3964
• Pmid: 35834886
• Language: English
• Keywords: FFR; Antiviral therapy; COVID-19; Nitazoxanide; SARS-CoV-2; Animal model; Pre-clinical research