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Synthesis of a Novel Class of 1,3-oxathiolane Nucleoside Derivatives of T- 705 and Evaluation of Their Anti-influenza A Virus and Anti-HIV Activity

[ Vol. 14 , Issue. 6 ]

Author(s):

Mingming Han, Xu Zhao, Xuedong Wu, Wei Huang, Xingzhou Li* and Fang Yu*   Pages 595 - 603 ( 9 )

Abstract:


Background: T-705 (Favipiravir) is a broad spectrum antiviral agent approved for stockpiling in Japan and currently in Phase 3 testing in the United States. Against influenza, it acts as a prodrug, converted intracellularly to selectively inhibit viral RNA-dependent RNA polymerase or similar enzymes. This is regarded as a novel antiviral mechanism of action, reducing crossresistance to other existing anti-influenza drugs.

Objective: To develop new analogs, a class of 1,3-oxathiolane nucleoside derivatives of T-705 was designed and synthesized in this work.

Results: Anti-influenza activity and Anti-HIV activity of these compounds were evaluated. Compound 1a displayed activity against A H1N1 with an IC50 of 40.4 µmol/L. Compound 1b showed weak activity against HIV with a viral suppression rate of 70-80% at 30 µmol/L.

Conclusion: A class of 1,3-oxathiolane nucleoside derivatives of T-705 was designed and synthesized, and one of them was identified as a novel scaffold against viral infection.

Keywords:

Nucleotide analog, favipiravi, anti-influenza, anti-HIV, 1, 3-oxathiolane nucleoside, viral enzymes.

Affiliation:

College of Chemistry, Chemical Engineering and Environmental Engineering, Liaoning Shihua University, Fushun 113001, Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, Forencic Science Department, Guangdong Police College, Guangzhou 510230, College of Chemistry, Chemical Engineering and Environmental Engineering, Liaoning Shihua University, Fushun 113001, Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, College of Chemistry, Chemical Engineering and Environmental Engineering, Liaoning Shihua University, Fushun 113001

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