tetano
Editor, Senior Moderator
J Mol Graph Model. 2012 Jul 4;38C:148-154. doi: 10.1016/j.jmgm.2012.06.007. [Epub ahead of print]
Binding pattern of the long acting neuraminidase inhibitor laninamivir towards influenza A subtypes H5N1 and pandemic H1N1.
Meeprasert A, Khuntawee W, Kamlungsua K, Nunthaboot N, Rungrotmongkol T, Hannongbua S.
Source
Computational Chemistry Unit Cell, Department of Chemistry, Faculty of Science, Chulalongkorn University, 254 Phayathai Road, Patumwan, Bangkok 10330, Thailand.
Abstract
Influenza A H5N1 and pH1N1 viruses have broadly emerged and become widespread in various countries around the world. Oseltamivir, the most commonly used antiviral drug against the seasonal and pandemic influenza viruses, is targeted at the viral neuraminidase (NA), but some isolates of this virus have become highly resistant to this drug. The novel long-acting drug, laninamivir, was recently developed to inhibit influenza A and B viruses of either the wild-type (WT) or the oseltamivir resistant mutant of NA. To understand the high efficiency of laninamivir, all-atom molecular dynamics simulations were performed on the WT and H274Y mutant of H5N1 and pH1N1 NAs with laninamivir bound. As a result, the novel drug was found to directly interact with 11 binding residues mainly through salt bridge and hydrogen bond formation (as also seen by electrostatic contribution). These are comprised of 7 of the catalytic residues (R118, D151, R152, R224, E276, R292 and R371), and 4 of the framework residues (E119, W178, E227 and E277). Laninamivir showed a similar binding pattern to all four NAs, but strong hydrogen bonding interactions were only found in the WT strain, with a slightly lowered contribution at some drug contact residues being observed in the H274Y mutation. This is in good agreement with the experimental data that the H274Y mutant has a small increase (1.3-7.5-fold, which was not statistically significant) in the IC(50) value of laninamivir.
Copyright ? 2012 Elsevier Inc. All rights reserved.
PMID:
23079644
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23079644
Binding pattern of the long acting neuraminidase inhibitor laninamivir towards influenza A subtypes H5N1 and pandemic H1N1.
Meeprasert A, Khuntawee W, Kamlungsua K, Nunthaboot N, Rungrotmongkol T, Hannongbua S.
Source
Computational Chemistry Unit Cell, Department of Chemistry, Faculty of Science, Chulalongkorn University, 254 Phayathai Road, Patumwan, Bangkok 10330, Thailand.
Abstract
Influenza A H5N1 and pH1N1 viruses have broadly emerged and become widespread in various countries around the world. Oseltamivir, the most commonly used antiviral drug against the seasonal and pandemic influenza viruses, is targeted at the viral neuraminidase (NA), but some isolates of this virus have become highly resistant to this drug. The novel long-acting drug, laninamivir, was recently developed to inhibit influenza A and B viruses of either the wild-type (WT) or the oseltamivir resistant mutant of NA. To understand the high efficiency of laninamivir, all-atom molecular dynamics simulations were performed on the WT and H274Y mutant of H5N1 and pH1N1 NAs with laninamivir bound. As a result, the novel drug was found to directly interact with 11 binding residues mainly through salt bridge and hydrogen bond formation (as also seen by electrostatic contribution). These are comprised of 7 of the catalytic residues (R118, D151, R152, R224, E276, R292 and R371), and 4 of the framework residues (E119, W178, E227 and E277). Laninamivir showed a similar binding pattern to all four NAs, but strong hydrogen bonding interactions were only found in the WT strain, with a slightly lowered contribution at some drug contact residues being observed in the H274Y mutation. This is in good agreement with the experimental data that the H274Y mutant has a small increase (1.3-7.5-fold, which was not statistically significant) in the IC(50) value of laninamivir.
Copyright ? 2012 Elsevier Inc. All rights reserved.
PMID:
23079644
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23079644