Development of Novel Anti-influenza Thiazolides with Relatively Broad-Spectrum Antiviral Potentials

Author:

Zhao Lei1,Yan Yunzheng1,Dai Qingsong1,Li Xingzhou1,Xu Ke2,Zou Gang3,Yang Keyu4,Li Wei1,Guo Xiaojia1,Yang Jingjing1,Li Yuexiang1,Xia Qing4,Cao Ruiyuan1,Zhong Wu1

Affiliation:

1. National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, People’s Republic of China

2. State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of China

3. Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, People’s Republic of China

4. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China

Abstract

Seasonal and pandemic influenza causes 650,000 deaths annually in the world. The emergence of drug resistance to specific anti-influenza virus drugs such as oseltamivir and baloxavir marboxil highlights the urgency of novel anti-influenza chemical entity discovery. In this study, we report a series of novel thiazolides derived from an FDA-approved drug, nitazoxanide, with antiviral activity against influenza and a broad range of viruses. The preferred candidates 4a and 4d showed significantly enhanced anti-influenza virus potentials, with 10-fold improvement compared to results with nitazoxanide, and were effective against a variety of influenza virus subtypes including oseltamivir-resistant strains.

Funder

China Postdoctoral Science Foundation

MOST | National Major Science and Technology Projects of China

National Natural Science Foundation of China

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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