Author(s)

Jinxi Liao¹, Huimin Cheng², Junting Wan¹, Panyu Chen¹, Yingjun Li^2,3, Ke Ding², Micky D. Tortorella¹, Zhengchao Tu^1*, Yanmei Zhang^1*

¹Drug Discovery Pipeline, Guangzhou Institutes of Biomedicine and Health, Science City, Guangzhou, China.
²Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
³University of Chinese Academy of Sciences, Beijing, China.

Virus nucleoprotein (NP) is an emerging target for drug development for Influenza. We designed benzamide derivatives as new inhibitors of NP that demonstrate good potency in blocking influenza A. Screening revealed that compound 39 was the most potent molecule in the series, exhibiting IC₅₀ values of 0.46 and 0.27 μM in blocking the replication of H3N2 (A/HK/8/68) and (A/WSN/33) influenza A viral strains. The observed inhibition of viral replication correlated well with cytopathic protection. Furthermore, based on computational analysis and fluorescence microscopy, it was determined that compound 39 inhibited nuclear accumulation by targeting influenza A viral nucleoproteins. Finally, the rodent pharmacokinetic profile of compound 32 displayed half-life of greater than 4 hours and bioavailability greater than 20%, suggesting this class of molecules had drug-like properties.

Benzamides, Nucleoprotein, Anti-Influenza, NP Inhibitors, Nucleozin

Liao, J. , Cheng, H. , Wan, J. , Chen, P. , Li, Y. , Ding, K. , Tortorella, M. , Tu, Z. and Zhang, Y. (2016) Evaluation of Benzamide Derivatives as New Influenza A Nucleoprotein Inhibitors. Open Journal of Medicinal Chemistry, 6, 43-50. doi: 10.4236/ojmc.2016.63004.