Nitazoxanide | Antiviral and antiparasitic agent / Inhibits Wnt signaling

Nitazoxanide (55981-09-4) is a clinically relevant antiparasitic agent.¹It 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 Its antiparasitic activity is believed to be due to inhibition of pyruvate:ferredoxin/flavodoxin oxidoreductases.³ Antiviral activity involves activation of protein kinase activated by double-stranded RNA (PKR) leading to phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α).⁴ Nitazoxanide 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

References/Citations

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; Gastroenterology 137 1827
5) Qu et al. (2018), Small molecule promotes β-catenin citrullination and inhibits Wnt signaling in cancer; Nat. Chem. Biol. 14 94