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dc.creatorMihajlović, Marija
dc.creatorMitrašinović, Petar M.
dc.date.accessioned2023-04-21T11:00:19Z
dc.date.available2023-04-21T11:00:19Z
dc.date.issued2009
dc.identifier.issn0352-5139
dc.identifier.urihttps://ritnms.itnms.ac.rs/handle/123456789/153
dc.description.abstractIn the context of the recent pandemic threat by the worldwide spread of H5N1 avian influenza, novel insights into the mechanism of ligand binding and interaction between various inhibitors (zanamivir - ZMV, oseltamivir - OTV, 2,3-didehydro-2-deoxy-N-acetylneuraminic acid - DANA, peramivir - PMV) and neuraminidases (NA) are of vital importance for the structure-based design of new anti-viral drugs. To address this issue, three-dimensional models of H5N1-NA and N9-NA were generated by homology modeling. Traditional residues within the active site throughout the family of NA protein structures were found to be highly conserved in H5N1-NA. A subtle variation between lipophilic and hydrophilic environments in H5N1-NA with respect to N9-NA was observed, thus shedding more light on the high resistance of some H5N1 strains to various NA inhibitors. Based on these models, an ArgusLab4/AScore flexible docking study was performed. The conformational differences between OTV bound to H5N1-NA and OTV bound to N9-NA were structurally identified and quantified. A slight difference of less than 1 kcal mol(-1) between the OTV-N9 and OTV-N1 binding free energies is in agreement with the experimentally predicted free energy difference. The conformational differences between ZMV and OTV bound to either H5N1-NA or N9-NA were structurally identified. The binding free energies of the ZMV complexes, being slightly higher than those of OTV, are not in agreement with what was previously proposed using homology modeling. The differences between-ZMV and OTV are suggested to be ascribed to the presence/absence of Asn 166 in the active cavity of ZMV/OTV in H5N1-NA, and to the presence/absence of Ser165 in the binding site of ZMV/OTV in N9-NA. The charge distribution was evaluated using the semi-empirical AMI method. The trends of the AMI charges of the ZMV and OTV side chains in the complexes deviate from those previously reported.en
dc.publisherSrpsko hemijsko društvo, Beograd
dc.rightsopenAccess
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceJournal of the Serbian Chemical Society
dc.subjectzanamiviren
dc.subjectoseltamiviren
dc.subjecthomology modelingen
dc.subjectH5N1 avian influenza virus neuraminidaseen
dc.subjectArgus Lab 4.0 dockingen
dc.titleSome novel insights into the binding of oseltamivir and zanamivir to H5N1 and N9 influenza virus neuraminidases: a homology modeling and flexible docking studyen
dc.typearticle
dc.rights.licenseBY-NC-ND
dc.citation.epage13
dc.citation.issue1
dc.citation.other74(1): 1-13
dc.citation.rankM23
dc.citation.spage1
dc.citation.volume74
dc.identifier.doi10.2298/JSC0901001M
dc.identifier.fulltexthttps://ritnms.itnms.ac.rs/bitstream/id/26/150.pdf
dc.identifier.rcubconv_555
dc.identifier.scopus2-s2.0-68849094171
dc.identifier.wos000263036400001
dc.type.versionpublishedVersion


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