Computational investigation of oseltamivir resistance in influenza A (H5N1) virus
Identifieur interne : 001815 ( Istex/Corpus ); précédent : 001814; suivant : 001816Computational investigation of oseltamivir resistance in influenza A (H5N1) virus
Auteurs : V. Karthick ; K. RamanathanSource :
- 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
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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><istex><corpusName>springer-journals</corpusName><author><json:item><name>V. Karthick</name><affiliations><json:string>Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology, 632014, Vellore, Tamil Nadu, India</json:string></affiliations></json:item><json:item><name>K. 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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. 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Technology</OrgName><OrgAddress><City>Vellore</City><Postcode>632014</Postcode><State>Tamil Nadu</State><Country Code="IN">India</Country></OrgAddress></Affiliation></AuthorGroup><Abstract ID="Abs1" Language="En" OutputMedium="All"><Heading>Abstract</Heading><Para>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.</Para></Abstract><KeywordGroup Language="En" OutputMedium="All"><Heading>Keywords</Heading><Keyword>Neuraminidase</Keyword><Keyword>Oseltamivir-resistance</Keyword><Keyword>Molecular docking</Keyword><Keyword>Molecular dynamic simulation</Keyword></KeywordGroup></ArticleHeader><NoBody></NoBody></Article></Issue></Volume></Journal></Publisher></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Computational investigation of oseltamivir resistance in influenza A (H5N1) virus</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Computational investigation of oseltamivir resistance in influenza A (H5N1) virus</title></titleInfo><name type="personal"><namePart type="given">V.</namePart><namePart type="family">Karthick</namePart><affiliation>Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology, 632014, Vellore, Tamil Nadu, India</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">K.</namePart><namePart type="family">Ramanathan</namePart><affiliation>Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology, 632014, Vellore, Tamil Nadu, India</affiliation><affiliation>E-mail: kramanathan@vit.ac.in</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="OriginalPaper" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>Springer US; http://www.springer-ny.com</publisher><place><placeTerm type="text">New York</placeTerm></place><dateCreated encoding="w3cdtf">2012-09-22</dateCreated><dateIssued encoding="w3cdtf">2013-12-01</dateIssued><copyrightDate encoding="w3cdtf">2013</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><abstract 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.</abstract><note>Original Research</note><subject lang="en"><genre>Keywords</genre><topic>Neuraminidase</topic><topic>Oseltamivir-resistance</topic><topic>Molecular docking</topic><topic>Molecular dynamic simulation</topic></subject><relatedItem type="host"><titleInfo><title>Medicinal Chemistry Research</title></titleInfo><titleInfo type="abbreviated"><title>Med Chem Res</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>Springer</publisher><dateIssued encoding="w3cdtf">2013</dateIssued><copyrightDate encoding="w3cdtf">2013</copyrightDate></originInfo><subject><genre>Journal-Subject-Collection</genre><topic authority="SpringerSubjectCodes" authorityURI="SC3">Biomedical and Life Sciences</topic></subject><classification authority="Journal-SubjectCollection-Code">SC3</classification><subject><genre>Journal-Subject-Group</genre><topic authority="SpringerSubjectCodes" authorityURI="SCB">Biomedicine</topic><topic authority="SpringerSubjectCodes" authorityURI="SCB21007">Pharmacology/Toxicology</topic><topic authority="SpringerSubjectCodes" authorityURI="SCL14005">Biochemistry, general</topic><topic authority="SpringerSubjectCodes" authorityURI="SCL16008">Cell Biology</topic></subject><identifier type="ISSN">1054-2523</identifier><identifier type="eISSN">1554-8120</identifier><identifier type="JournalID">44</identifier><identifier type="IssueArticleCount">51</identifier><identifier type="VolumeIssueCount">12</identifier><part><date>2013</date><detail type="volume"><number>22</number><caption>vol.</caption></detail><detail type="issue"><number>12</number><caption>no.</caption></detail><extent unit="pages"><start>5764</start><end>5771</end></extent></part><recordInfo><recordOrigin>Springer Science+Business Media New York, 2013</recordOrigin></recordInfo></relatedItem><identifier type="istex">FB1734BC5430A4AEA65961A48193D4E3BE6FB2A5</identifier><identifier type="ark">ark:/67375/VQC-M6TH2VKD-R</identifier><identifier type="DOI">10.1007/s00044-013-0551-2</identifier><identifier type="ArticleID">551</identifier><identifier type="ArticleID">s00044-013-0551-2</identifier><accessCondition type="use and reproduction" contentType="copyright">Springer Science+Business Media New York, 2013</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-3XSW68JL-F">springer</recordContentSource><recordOrigin>Converted from (version 1.2.14) to MODS version 3.6.</recordOrigin><recordCreationDate encoding="w3cdtf">2020-05-28</recordCreationDate></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-M6TH2VKD-R/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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