Nitazoxanide (55981-09-4) has been found to inhibit Wnt signaling independent of adenomatous polyposis coli (APC) – it targets peptidyl arginine deiminase 2 (PAD2) resulting in increased citrullination of b-catenin.¹   Nitazoxanide is a clinically relevant antiparasitic agent.² It 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.³ Its antiparasitic activity is believed to be due to inhibition of pyruvate:ferredoxin/flavodoxin oxidoreductases.⁴ Antiviral activity involves activation of protein kinase activated by double-stranded RNA (PKR) leading to phosphorylation of eukaryotic initiation factor 2 alpha (eIF2a).⁵

References/Citations:

• Qu et al. (2018), Small molecule promotes b-catenin citrullination and inhibits Wnt signaling in cancer; Nat.Chem.Biol. 14 94
• White (2004) Nitazoxanide: a new broad spectrum antiparasitic agent; Expert Rev.Anti.Infect.Ther. 2 43
• Rossignol (2014) Nitazoxanide: a first-in-class broad-spectrum antiviral agent; Antiviral Res. 110 94
• Hoffman et al. (2007) Antiparasitic Drug Nitazoxanide Inhibits the Pyruvate Oxidoreductases of Helicobacter pylori, Selected anaerobic Bacteria and Parasites, and Campylobacter jejuni; Agents Chemother. 51 868
• 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