Exploration of binding and inhibition mechanism of a small molecule inhibitor of influenza virus H1N1 hemagglutinin by molecular dynamics simulation
Abstract Influenza viruses are a major public health threat worldwide. The influenza hemagglutinin (HA) plays an essential role in the virus life cycle. Due to the high conservation of the HA stem region, it has become an especially attractive target for inhibitors for therapeutics. In this study, m...
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2017
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oai:doaj.org-article:b43afec578b34601b761db4bdc63eecc2021-12-02T12:32:55ZExploration of binding and inhibition mechanism of a small molecule inhibitor of influenza virus H1N1 hemagglutinin by molecular dynamics simulation10.1038/s41598-017-03719-42045-2322https://doaj.org/article/b43afec578b34601b761db4bdc63eecc2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03719-4https://doaj.org/toc/2045-2322Abstract Influenza viruses are a major public health threat worldwide. The influenza hemagglutinin (HA) plays an essential role in the virus life cycle. Due to the high conservation of the HA stem region, it has become an especially attractive target for inhibitors for therapeutics. In this study, molecular simulation was applied to study the mechanism of a small molecule inhibitor (MBX2329) of influenza HA. Behaviors of the small molecule under neutral and acidic conditions were investigated, and an interesting dynamic binding mechanism was found. The results suggested that the binding of the inhibitor with HA under neutral conditions facilitates only its intake, while it interacts with HA under acidic conditions using a different mechanism at a new binding site. After a series of experiments, we believe that binding of the inhibitor can prevent the release of HA1 from HA2, further maintaining the rigidity of the HA2 loop and stabilizing the distance between the long helix and short helices. The investigated residues in the new binding site show high conservation, implying that the new binding pocket has the potential to be an effective drug target. The results of this study will provide a theoretical basis for the mechanism of new influenza virus inhibitors.Shanshan GuanTianao WangZiyu KuaiMengdan QianXiaopian TianXiuqi ZhangYongjiao YuSong WangHao ZhangHao LiWei KongYaming ShanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) |
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Medicine R Science Q Shanshan Guan Tianao Wang Ziyu Kuai Mengdan Qian Xiaopian Tian Xiuqi Zhang Yongjiao Yu Song Wang Hao Zhang Hao Li Wei Kong Yaming Shan Exploration of binding and inhibition mechanism of a small molecule inhibitor of influenza virus H1N1 hemagglutinin by molecular dynamics simulation |
| description |
Abstract Influenza viruses are a major public health threat worldwide. The influenza hemagglutinin (HA) plays an essential role in the virus life cycle. Due to the high conservation of the HA stem region, it has become an especially attractive target for inhibitors for therapeutics. In this study, molecular simulation was applied to study the mechanism of a small molecule inhibitor (MBX2329) of influenza HA. Behaviors of the small molecule under neutral and acidic conditions were investigated, and an interesting dynamic binding mechanism was found. The results suggested that the binding of the inhibitor with HA under neutral conditions facilitates only its intake, while it interacts with HA under acidic conditions using a different mechanism at a new binding site. After a series of experiments, we believe that binding of the inhibitor can prevent the release of HA1 from HA2, further maintaining the rigidity of the HA2 loop and stabilizing the distance between the long helix and short helices. The investigated residues in the new binding site show high conservation, implying that the new binding pocket has the potential to be an effective drug target. The results of this study will provide a theoretical basis for the mechanism of new influenza virus inhibitors. |
| format |
article |
| author |
Shanshan Guan Tianao Wang Ziyu Kuai Mengdan Qian Xiaopian Tian Xiuqi Zhang Yongjiao Yu Song Wang Hao Zhang Hao Li Wei Kong Yaming Shan |
| author_facet |
Shanshan Guan Tianao Wang Ziyu Kuai Mengdan Qian Xiaopian Tian Xiuqi Zhang Yongjiao Yu Song Wang Hao Zhang Hao Li Wei Kong Yaming Shan |
| author_sort |
Shanshan Guan |
| title |
Exploration of binding and inhibition mechanism of a small molecule inhibitor of influenza virus H1N1 hemagglutinin by molecular dynamics simulation |
| title_short |
Exploration of binding and inhibition mechanism of a small molecule inhibitor of influenza virus H1N1 hemagglutinin by molecular dynamics simulation |
| title_full |
Exploration of binding and inhibition mechanism of a small molecule inhibitor of influenza virus H1N1 hemagglutinin by molecular dynamics simulation |
| title_fullStr |
Exploration of binding and inhibition mechanism of a small molecule inhibitor of influenza virus H1N1 hemagglutinin by molecular dynamics simulation |
| title_full_unstemmed |
Exploration of binding and inhibition mechanism of a small molecule inhibitor of influenza virus H1N1 hemagglutinin by molecular dynamics simulation |
| title_sort |
exploration of binding and inhibition mechanism of a small molecule inhibitor of influenza virus h1n1 hemagglutinin by molecular dynamics simulation |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/b43afec578b34601b761db4bdc63eecc |
| work_keys_str_mv |
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1718393941439545344 |