The FDA-approved drug nitazoxanide is a potent inhibitor of human seasonal coronaviruses acting at postentry level: effect on the viral spike glycoprotein

Frontiers in Microbiology

Microbiology

Silvia Santopolo¹  Sara Piacentini¹  Silvia Pauciullo¹  Simone La Frazia¹  Anna Riccio¹  M. Gabriella Santoro²  Antonio Rossi³  Jean-Francois Rossignol⁴ 

[1] Department of Biology, University of Rome Tor Vergata, Rome, Italy;Department of Biology, University of Rome Tor Vergata, Rome, Italy;Institute of Translational Pharmacology, CNR, Rome, Italy;Institute of Translational Pharmacology, CNR, Rome, Italy;Romark Institute of Medical Research, Tampa, FL, United States;

关键词: antiviral;    HCoV-229E;    HCoV-OC43;    HCoV-NL63;    nitazoxanide;    spike glycoprotein;   

DOI  :  10.3389/fmicb.2023.1206951

 received in 2023-04-16, accepted in 2023-08-07,  发布年份 2023

来源: Frontiers

【 摘 要 】

Coronaviridae is recognized as one of the most rapidly evolving virus family as a consequence of the high genomic nucleotide substitution rates and recombination. The family comprises a large number of enveloped, positive-sense single-stranded RNA viruses, causing an array of diseases of varying severity in animals and humans. To date, seven human coronaviruses (HCoV) have been identified, namely HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1, which are globally circulating in the human population (seasonal HCoV, sHCoV), and the highly pathogenic SARS-CoV, MERS-CoV and SARS-CoV-2. Seasonal HCoV are estimated to contribute to 15–30% of common cold cases in humans; although diseases are generally self-limiting, sHCoV can sometimes cause severe lower respiratory infections and life-threatening diseases in a subset of patients. No specific treatment is presently available for sHCoV infections. Herein we show that the anti-infective drug nitazoxanide has a potent antiviral activity against three human endemic coronaviruses, the Alpha-coronaviruses HCoV-229E and HCoV-NL63, and the Beta-coronavirus HCoV-OC43 in cell culture with IC50 ranging between 0.05 and 0.15 μg/mL and high selectivity indexes. We found that nitazoxanide does not affect HCoV adsorption, entry or uncoating, but acts at postentry level and interferes with the spike glycoprotein maturation, hampering its terminal glycosylation at an endoglycosidase H-sensitive stage. Altogether the results indicate that nitazoxanide, due to its broad-spectrum anti-coronavirus activity, may represent a readily available useful tool in the treatment of seasonal coronavirus infections.

【 授权许可】

Unknown   
Copyright © 2023 Piacentini, Riccio, Santopolo, Pauciullo, La Frazia, Rossi, Rossignol and Santoro.