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dc.creatorMihajlović, Marija
dc.creatorMitrašinović, Petar M.
dc.date.accessioned2023-04-21T10:59:10Z
dc.date.available2023-04-21T10:59:10Z
dc.date.issued2008
dc.identifier.issn0301-4622
dc.identifier.urihttps://ritnms.itnms.ac.rs/handle/123456789/143
dc.description.abstractIn the context of a recent pandemic threat by the worldwide spread of H5N1 avian influenza, the high resistance of H5N1 virus to the most widely used commercial drug, oseltarnivir (Tamiflu), is currently an important research topic. Herein, molecular bases of the mechanism of H5N1 NA resistance to orseltarnivir were elucidated using a computational approach in a systematic fashion. Using the crystal structure of the complex of H5N1 NAwith OTV (PDB ID: 2hu0) as the starting point, the question, how mutations at His274 by both smaller side chain (Gly, Set, Asn, Gln) and larger side chain (Phe, Tyr) residues influence the sensitivity of N1 to orseltarnivir, was addressed and correlated with the experimental data. The smaller side chain residue mutations of His;274 resulted in slightly enhanced or unchanged NA sensitivity to OTV, while His274Phe and His274Tyr reduced the susceptibility of OTV to N1. In contrast to the binding free energies, the net charges of Glu276 and Arg224, making charge-charge interactions with Glu276, were established to be more sensitive to detecting subtle conformational differences induced at the key residue Glu276 by the His274X mutations. This study provides deeper insights into the possibility of developing viable drug-resistant mutants.en
dc.publisherElsevier Science Bv, Amsterdam
dc.rightsrestrictedAccess
dc.sourceBiophysical Chemistry
dc.subjectresistanceen
dc.subjectoseltamiviren
dc.subjectmutantsen
dc.subjectinfluenza a virusen
dc.subjectH5N1 neuraminidaseen
dc.titleAnother look at the molecular mechanism of the resistance of H5N1 influenza A virus neuraminidase (NA) to oseltamivir (OTV)en
dc.typearticle
dc.rights.licenseARR
dc.citation.epage158
dc.citation.issue2-3
dc.citation.other136(2-3): 152-158
dc.citation.rankM22
dc.citation.spage152
dc.citation.volume136
dc.identifier.doi10.1016/j.bpc.2008.06.003
dc.identifier.pmid18584938
dc.identifier.rcubconv_546
dc.identifier.scopus2-s2.0-46149126359
dc.identifier.wos000257821400012
dc.type.versionpublishedVersion


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