Inhibitory potency of flavonoid derivatives on influenza virus neuraminidase |
| |
| Institution: | 1. College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China;2. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China;1. Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea;2. Choong Ang Vaccine Laboratory, 59-3 Hwaam-dong, Yuseong-gu, Daejeon 305-348, Republic of Korea;3. Marine Bio Research Center, Department of Life Science, Chosun University, Gwangju 501-759, Republic of Korea |
| |
| Abstract: | The constant risk of emerging new influenza virus strains that are resistant to established inhibitors like oseltamivir leaves influenza neuraminidase (NA) a prominent target for drug design. The inhibitory activity of several flavonoid derivatives was experimentally tested in comparison to oseltamivir for the NA expressed by the seasonal influenza virus strains A/California/7/09 (A(H1N1)pdm09), A/Perth/16/09 (A(H3N2)), and B/Brisbane/60/08. IC50 values of polyphenols confirmed moderate inhibition in the μM range. Structurally, the amount and site of glycosylation of tested flavonoids have no significant influence on their inhibitory potency. In a pharmacophore-based docking approach the structure–activity relationship was evaluated. Molecular dynamics simulations revealed highly flexible parts of the enzyme and the contribution of salt bridges to the structural stability of NA. The findings of this study elucidate the impact of flavonoids on viral neuraminidase activity and the analysis of their modes of action provide valuable information about the mechanism of NA inhibition. |
| |
| Keywords: | Influenza Neuraminidase Flavonoids Molecular dynamics Docking |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
