tetano
Editor, Senior Moderator
J Mol Model. 2012 Jan 27. [Epub ahead of print]
Computational study on new natural polycyclic compounds of H1N1 influenza virus neuraminidase.
Wang Y, Wu D, Yu D, Wang Z, Tian L, Wang Y, Han W, Fang X.
Source
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, 2699 Qianjin Street, Changchun, 130012, China.
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.
PMID:
22278046
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22278046
Computational study on new natural polycyclic compounds of H1N1 influenza virus neuraminidase.
Wang Y, Wu D, Yu D, Wang Z, Tian L, Wang Y, Han W, Fang X.
Source
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, 2699 Qianjin Street, Changchun, 130012, China.
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.
PMID:
22278046
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22278046