Antiviral, antiparasitic. Inhibits the SARS-CoV-2 at low-micromolar concentration. Liu et al. ACS Cent. Sci., 6:315-331, Mar 12 2020, https://doi.org/10.1021/acscentsci.0c00272; Wang et al. Cell Res 30:269–271, Feb 4 2020, https://doi.org/10.1038/s41422-020-0282-0.
Biochemicals & reagents
1) White (2004) Nitazoxanide: a new broad spectrum antiparasitic agent; Expert Rev. Anti. Infect. Ther. 2 43 2) Rossignol (2014) Nitazoxanide: a first-in-class broad-spectrum antiviral agent; Antiviral Res. 110 94 3) Hoffman et al. (2007) Antiparasitic Drug Nitazoxanide Inhibits the Pyruvate Oxidoreductases of Helicobacter pylori, Selected anaerobic Bacteria and Parasites, and Campylobacter jejuni; Antimicrob. Agents Chemother. 51 868 4) Elazar et al. (2009), The anti-hepatitis C agent nitazoxanide induces phosphorylation of eukaryotic initiation factor 2alpha via protein kinase activated by double-stranded RNA activation; Gastorenterology 137 1827 5) Qu et al. (2018), Small molecule promotes β-catenin citrullination and inhibits Wnt signaling in cancer; Nat. Chem. Biol. 14 94
Nitazoxanide is a clinically relevant antiparasitic agent (1) and has since been repurposed as a broad-spectrum antiviral agent that is active against many RNA and DNA viruses including influenza, Hepatitis B and C, RSV, coronavirus, dengue and others (2). It's antiparasitic activity is believed to be due to the inhibition of pyruvate:ferredoxin/flavodoxin oxidoreductases (3). It's antiviral activity involves activation of protein kinase activated by double-stranded RNA (PKR) leading to phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) (4). This compound has also been found to inhibit Wnt signaling independent of adenomatous polyposis coli (APC) – it targets peptidyl arginine deiminase 2 (PAD2) resulting in increased citrullination of β-catenin (5).