Citation: Lin Li, Sheng Hai Chang, Jun Feng Xiang, Qian Li, Huan Huan Liang, Ya Lin Tang, Ying Fang Liu. NMR identification of anti-influenza lead compound targeting at PA_C subunit of H5N1 polymerase[J]. Chinese Chemical Letters, ;2012, 23(1): 89-92. doi: 10.1016/j.cclet.2011.09.006 shu

NMR identification of anti-influenza lead compound targeting at PA_C subunit of H5N1 polymerase

a State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China;
b National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;
c Graduate University, Chinese Academy of Sciences, Beijing 100049, China

Received Date: 17 May 2011

Fund Project: Experimental section is available in Supporting Information. This work was supported by the National Natural Science Foundation of China (No. 81072576) to Y.L. Tang, the National Natural Science Foundation of China (No. 30925011) and the Ministry of Science and Technology 863 Project (No. 2006AA02A314) to Y.F. Liu.

PA_C subunit from avian influenza (H5N1) viral RNA polymerase was used in this work as a target in the screening for anti-influenza agents from licorice-derived compounds. As a result, 18β-glycyrrhetinic acid was suggested to be PA_C ligand by flexible docking, and was then confirmed by relaxation-edited NMR. The result of ApG primer extension assay indicated that this PA_C ligand can inhibit the polymerase activity, and thus may potentially be valuable as anti-influenza lead compound. This work validated the possibility of screening polymerase inhibitors by using PA_C as a target, and provided a starting point for the further discovery of new anti-influenza drugs.
- PA_C,
- RNA polymerase inhibitor,
- Anti-influenza agent,
- Licorice-derived compounds
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