Computational investigation of oseltamivir resistance in influenza A (H5N1) virus
Identifieur interne : 001815 ( Istex/Curation ); précédent : 001814; suivant : 001816Computational investigation of oseltamivir resistance in influenza A (H5N1) virus
Auteurs : V. Karthick [Inde] ; K. Ramanathan [Inde]Source :
- Medicinal Chemistry Research [ 1054-2523 ] ; 2013.
Abstract
Abstract: Oseltamivir is the most effective antiviral drug used for the treatment and prevention of influenza A infections. Neuraminidase is the principal target for treating patients with H5N1 infection. Until recently, only a low prevalence of neuraminidase inhibitors (NAIs) resistance (<1 %) had been detected in circulating viruses. However, there have been reports of significant numbers of influenza A (H5N1) strains with a H274Y neuraminidase mutation that was highly resistant to the NAI, oseltamivir. In this study, we used molecular docking and molecular dynamics (MD) approach to characterize the effect of H274Y mutation in drug–target interactions. Docking results suggest that oseltamivir was found to adopt the most promising conformations to the wild type NA (WT) by identifying the guanidinium side chain of R-156 and R-152 as a prospective partner for making polar contacts as compared to the mutant type NA. The MD results showed that the average atom, especially atoms of the wild type NA–oseltamivir complex, movements were small, displayed fast convergence of energy and charges in geometry. This highlights the stable binding of the oseltamivir with wild type NA as compared to mutant type NA. Overall, our study may be helpful for the rational design of more powerful, selective, and more robust NAI against drug-resistant H274Y mutation.
Url:
DOI: 10.1007/s00044-013-0551-2
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: Pour aller vers cette notice dans l'étape Curation :001815
Links to Exploration step
ISTEX:FB1734BC5430A4AEA65961A48193D4E3BE6FB2A5Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Computational investigation of oseltamivir resistance in influenza A (H5N1) virus</title><author><name sortKey="Karthick, V" sort="Karthick, V" uniqKey="Karthick V" first="V." last="Karthick">V. Karthick</name><affiliation wicri:level="1"><mods:affiliation>Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology, 632014, Vellore, Tamil Nadu, India</mods:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology, 632014, Vellore, Tamil Nadu</wicri:regionArea></affiliation></author><author><name sortKey="Ramanathan, K" sort="Ramanathan, K" uniqKey="Ramanathan K" first="K." last="Ramanathan">K. Ramanathan</name><affiliation wicri:level="1"><mods:affiliation>Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology, 632014, Vellore, Tamil Nadu, India</mods:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology, 632014, Vellore, Tamil Nadu</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>E-mail: kramanathan@vit.ac.in</mods:affiliation><country wicri:rule="url">Inde</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:FB1734BC5430A4AEA65961A48193D4E3BE6FB2A5</idno><date when="2013" year="2013">2013</date><idno type="doi">10.1007/s00044-013-0551-2</idno><idno type="url">https://api.istex.fr/ark:/67375/VQC-M6TH2VKD-R/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">001815</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001815</idno><idno type="wicri:Area/Istex/Curation">001815</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Computational investigation of oseltamivir resistance in influenza A (H5N1) virus</title><author><name sortKey="Karthick, V" sort="Karthick, V" uniqKey="Karthick V" first="V." last="Karthick">V. Karthick</name><affiliation wicri:level="1"><mods:affiliation>Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology, 632014, Vellore, Tamil Nadu, India</mods:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology, 632014, Vellore, Tamil Nadu</wicri:regionArea></affiliation></author><author><name sortKey="Ramanathan, K" sort="Ramanathan, K" uniqKey="Ramanathan K" first="K." last="Ramanathan">K. Ramanathan</name><affiliation wicri:level="1"><mods:affiliation>Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology, 632014, Vellore, Tamil Nadu, India</mods:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology, 632014, Vellore, Tamil Nadu</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>E-mail: kramanathan@vit.ac.in</mods:affiliation><country wicri:rule="url">Inde</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Medicinal Chemistry Research</title><title level="j" type="abbrev">Med Chem Res</title><idno type="ISSN">1054-2523</idno><idno type="eISSN">1554-8120</idno><imprint><publisher ref="https://scientific-publisher.data.istex.fr/ark:/67375/H02-SWLMH5L1-1">Springer US</publisher><pubPlace>New York</pubPlace><note type="URL">http://www.springer-ny.com</note><date type="published" when="2013">2013</date><biblScope unit="vol" from="22" to="22">22</biblScope><biblScope unit="issue" from="12" to="12">12</biblScope><biblScope unit="page" from="5764">5764</biblScope><biblScope unit="page" to="5771">5771</biblScope></imprint><idno type="ISSN">1054-2523</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1054-2523</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Oseltamivir is the most effective antiviral drug used for the treatment and prevention of influenza A infections. Neuraminidase is the principal target for treating patients with H5N1 infection. Until recently, only a low prevalence of neuraminidase inhibitors (NAIs) resistance (<1 %) had been detected in circulating viruses. However, there have been reports of significant numbers of influenza A (H5N1) strains with a H274Y neuraminidase mutation that was highly resistant to the NAI, oseltamivir. In this study, we used molecular docking and molecular dynamics (MD) approach to characterize the effect of H274Y mutation in drug–target interactions. Docking results suggest that oseltamivir was found to adopt the most promising conformations to the wild type NA (WT) by identifying the guanidinium side chain of R-156 and R-152 as a prospective partner for making polar contacts as compared to the mutant type NA. The MD results showed that the average atom, especially atoms of the wild type NA–oseltamivir complex, movements were small, displayed fast convergence of energy and charges in geometry. This highlights the stable binding of the oseltamivir with wild type NA as compared to mutant type NA. Overall, our study may be helpful for the rational design of more powerful, selective, and more robust NAI against drug-resistant H274Y mutation.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/PandemieGrippaleV1/Data/Istex/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001815 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Curation/biblio.hfd -nk 001815 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= PandemieGrippaleV1
|flux= Istex
|étape= Curation
|type= RBID
|clé= ISTEX:FB1734BC5430A4AEA65961A48193D4E3BE6FB2A5
|texte= Computational investigation of oseltamivir resistance in influenza A (H5N1) virus
}}
| This area was generated with Dilib version V0.6.34. |  |