title: Computational study on new natural polycyclic compounds of H1N1 influenza virus neuraminidase.
abstract: A new strain of influenza A (H1N1) virus is a major cause of morbidity and mortality around the world. The neuraminidase of the influenza virus has been the most potential target for the anti-influenza drugs such as oseltamivir and zanamivir. However, the emergence of drug-resistant variants of these drugs makes a pressing need for the development of new neuraminidase inhibitors for controlling illness and transmission. Here a 3D structure model of H1N1 avian influenza virus neuraminidase type 1 (N1) was constructed based on the structure of the template H5N1 avian influenza virus N1. Upon application of virtual screening technique for N1 inhibitors, two novel compounds (ZINC database ID: ZINC02128091, ZINC02098378) were found as the most favorable interaction energy with N1. Docking results showed that the compounds bound not only in the active pocket, but also in a new hydrophobic cave which contains Arg368, Trp399, Ile427, Pro431 and Lys432 of N1. Our result suggested that both of the screened compounds containing the hydrophobic group bring a strong conjugation effect with Arg293, Arg368 Lys432 of N1 by pi-pi interaction. However, the control inhibitors zanamivir and oseltamivir do not have this effect. The details of N1-compound binding structure obtained will be valuable for the development of a new anti-influenza virus agent.
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, 2699 Qianjin Street, Changchun, 130012, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Dahai
authors.initials: D
authors.lastname: Yu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Tian
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Han
authors.forename: Xuexun
authors.initials: X
authors.lastname: Fang
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry*; D020134:Catalytic Domain; D003198:Computer Simulation; D006860:Hydrogen Bonding; D053118:Influenza A Virus, H1N1 Subtype / Q000201:enzymology*; D008958:Models, Molecular; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D053139:Oseltamivir / Q000737:chemistry; D011083:Polycyclic Compounds / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D040681:Structural Homology, Protein; D013816:Thermodynamics; D053243:Zanamivir / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D011083:Polycyclic Compounds; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir