Structural analysis of the novel influenza A (H7N9) viral Neuraminidase interactions with current approved neuraminidase inhibitors Oseltamivir, Zanamivir, and Peramivir in the presence of mutation R289K

BMC Bioinformatics

Research

Xuchang Ouyang¹  Chinh Tran-To Su¹  Chee-Keong Kwoh¹  Jie Zheng² 

[1] Bioinformatics Research Center, School of Computer Engineering, Nanyang Technological University, 639798, Singapore;Bioinformatics Research Center, School of Computer Engineering, Nanyang Technological University, 639798, Singapore;Genome Institute of Singapore, Agency of Science, Technology, and Research (A*STAR), 138672, Biopolis, Singapore;

关键词: Influenza;    Avian Influenza;    Oseltamivir;    H7N9 Influenza;    Zanamivir;   

DOI  :  10.1186/1471-2105-14-S16-S7

来源: Springer

【 摘 要 】

BackgroundSince late March 2013, there has been another global health concern with a sudden wave of flu infections by a novel strain of avian influenza A (H7N9) virus in China. To-date, there have been more than 100 infections with 23 deaths. It is more worrying as this viral strain has never been detected in humans and only been found to be of low-pathogenicity. Currently, there are 3 effective neuraminidase inhibitors for this H7N9 virus strain, i.e. oseltamivir, zanamivir, and peramivir. These drugs have been used for treatment of the H7N9 influenza in China. However, how these inhibitors work and affect the binding cavity of the novel H7N9 neuraminidase in the presence of potential mutations has not been disclosed. In our study, we investigate steric effects and subsequently show the conformational restraints of the inhibitor-binding site of the non-mutated and mutated H7N9 neuraminidase structures to different drug compounds.ResultsCombination of molecular docking and Molecular Dynamics simulation reveal that zanamivir forms more favorable and stable complex than oseltamivir and peramivir when binding to the active site of the H7N9 neuraminidase. And it is likely that the novel influenza A (H7N9) virus adopts a higher probability to acquire resistance to peramivir than the other two inhibitors. Conformational changes induced by the mutation R289K causes loss of number of hydrogen bonds between the inhibitors and the H7N9 viral neuraminidase in 2 out of 3 complexes. In addition, our results of binding-affinity relationships of the 3 inhibitors with the viral neuraminidase proteins of previous pandemics (H1N1, H5N1) and the current novel H7N9 reflected the extent of binding effectiveness of the 3 inhibitors to the novel H7N9 neuraminidase.ConclusionsThe results are novel and specific for the A/Hangzhou/1/2013(H7N9) influenza strain. Furthermore, the protocol could be useful for further drug-binding analysis and prediction of future viral mutations to which the virus evolves through adaptation and acquires resistance to the current available drugs.

【 授权许可】

Unknown   
© Tran-To Su et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.