Nitazoxanide drug found to be a potent inhibitor of several human coronaviruses biorxivpreprint unitorvergata SARSCoV2 COVID19 Coronavirus Nitazoxanide
By Neha MathurJul 18 2022Reviewed by Aimee Molineux In a recent study posted to the bioRxiv* pre-print server, researchers evaluated the activity of nitazoxanide against human coronaviruses .
All sHCoVs use different host cell receptors; however, all initiate binding to host cells via the spike glycoprotein anchored in their viral envelope. Nitazoxanide, a second-generation thiazolide, has emerged as a new class of broad-spectrum antiviral drugs that acts at the postentry level to interfere with the S maturation. Also, its active metabolite tizoxanide demonstrated efficacy against several ribonucleic acid viruses, including rotavirus, hepatitis C, and influenza, in clinical trials.
They used cell culture with high selectivity indexes and half-maximal inhibitory concentration values between 0.05 and 0.15 µg/ml. First, the team inoculated human lung MRC-5 and monkey kidney LLC-MK2 cells with HCoVs 229E, OC43, and NL63 at the multiplicity of infection of 0.1 median tissue culture infectious dose /cell. Then, they treated these cells with different concentrations of nitazoxanide following the virus adsorption period.
Lastly, they assessed the effect of nitazoxanide on levels of the viral nucleocapsid and spike proteins. They used the immunoblotting technique to analyze the cells infected with 0.5 TCID50/cell of HCoV-OC43 at 24 hours post-infection and infectivity assay to determine the culture supernatants. Since NTZ treatment during virus adsorption did not affect HCoV replication, it indicated that nitazoxanide acted at a postentry level; additionally, it did not affect HCoVs adsorption, entry, or uncoating. Intriguingly, NTZ treatment at more than 0.1 µg/ml concentration altered S protein's electrophoretic mobility pattern. However, the authors observed no significant differences in N and S protein levels in NTZtreated cells.
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