Overview:

**COVID-19 RELATION**
Nitazoxanide is a broad-spectrum synthetic benzamide compound that is used as medicine for the treatment of various helminthic, protozoal, and viral infections. In-vitro analysis suggests that this compound inhibits replication of many members of the coronavirus family including MERS-Cov, BCoV, HECoV, and improves clinical outcomes by suppressing the overproduction of pro-inflammatory cytokines which is observed in patients with coronavirus infection. The clinical implications of this compound on SARS-CoV-2 is under investigation at the moment. **

Nitazoxanide is a clinically useful antiparasitic agent (1). 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 (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), targeting peptidyl arginine deiminase 2 (PAD2) resulting in increased citrullination of β-catenin (5).

References:

1. CA White Expert Rev. Anti. Infect. Ther. 2004 2:43

2. J-F Rossignol Antiviral Res. 2014 110:94

3. PS Hoffman et al. Antimicrob. Agents Chemother. 2007 51:868

4. M Elazar et al. Gastroenterology 2009 137:1827

5. Y Qu et al. Nat. Chem. Biol. 2018 14:94