In silico analysis of drug-resistant mutant of neuraminidase (N294S) against oseltamivir
Identifieur interne : 001100 ( Istex/Corpus ); précédent : 001099; suivant : 001101In silico analysis of drug-resistant mutant of neuraminidase (N294S) against oseltamivir
Auteurs : V. Karthick ; V. Shanthi ; R. Rajasekaran ; K. RamanathanSource :
- Protoplasma [ 0033-183X ] ; 2013-02-01.
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Abstract
Abstract: The recent H1N1 influenza pandemic has attracted worldwide attention due to the high infection rate. Oseltamivir is a new class of anti-viral agent approved for the treatment and prevention of influenza infections. The principal target for this drug is a virus surface glycoprotein, neuraminidase (NA), which facilitates the release of nascent virus and thus spreads infection. Until recently, only a low prevalence of neuraminidase inhibitor (NAI) resistance (<1 %) had been detected in circulating viruses. However, there have been reports of significant numbers of A (H1N1) influenza strains with a N294S neuraminidase mutation that was highly resistant to the NAI, oseltamivir. Hence, in the present study, we highlight the effect of point mutation-induced oseltamivir resistance in H1N1 subtype neuraminidases by molecular simulation approach. The docking analysis reveals that mutation (N294S) significantly affects the binding affinity of oseltamivir with mutant type NA. This is mainly due to the decrease in the flexibility of binding site residues and the difference in prevalence of hydrogen bonds in the wild and mutant structures. This study throws light on the possible effects of drug-resistant mutations on the large functionally important collective motions in biological systems.
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DOI: 10.1007/s00709-012-0394-6
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Oseltamivir is a new class of anti-viral agent approved for the treatment and prevention of influenza infections. The principal target for this drug is a virus surface glycoprotein, neuraminidase (NA), which facilitates the release of nascent virus and thus spreads infection. Until recently, only a low prevalence of neuraminidase inhibitor (NAI) resistance (<1 %) had been detected in circulating viruses. However, there have been reports of significant numbers of A (H1N1) influenza strains with a N294S neuraminidase mutation that was highly resistant to the NAI, oseltamivir. Hence, in the present study, we highlight the effect of point mutation-induced oseltamivir resistance in H1N1 subtype neuraminidases by molecular simulation approach. The docking analysis reveals that mutation (N294S) significantly affects the binding affinity of oseltamivir with mutant type NA. This is mainly due to the decrease in the flexibility of binding site residues and the difference in prevalence of hydrogen bonds in the wild and mutant structures. This study throws light on the possible effects of drug-resistant mutations on the large functionally important collective motions in biological systems.</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>V. Shanthi</name><affiliations><json:string>Industrial Biotechnology Division, School of Bio Sciences and Technology, Vellore Institute of Technology, 632014, Vellore, Tamil Nadu, India</json:string></affiliations></json:item><json:item><name>R. 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DisplayOrder="Western"><GivenName>K.</GivenName><FamilyName>Ramanathan</FamilyName></AuthorName><Contact><Phone>+91-416-2202546</Phone><Fax>+91-416-2243092</Fax><Email>kramanathan@vit.ac.in</Email></Contact></Author><Affiliation ID="Aff1"><OrgDivision>Bioinformatics Division, School of Bio Sciences and Technology</OrgDivision><OrgName>Vellore Institute of Technology</OrgName><OrgAddress><City>Vellore</City><Postcode>632014</Postcode><State>Tamil Nadu</State><Country Code="IN">India</Country></OrgAddress></Affiliation><Affiliation ID="Aff2"><OrgDivision>Industrial Biotechnology Division, School of Bio Sciences and Technology</OrgDivision><OrgName>Vellore Institute of 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>The recent H1N1 influenza pandemic has attracted worldwide attention due to the high infection rate. Oseltamivir is a new class of anti-viral agent approved for the treatment and prevention of influenza infections. The principal target for this drug is a virus surface glycoprotein, neuraminidase (NA), which facilitates the release of nascent virus and thus spreads infection. Until recently, only a low prevalence of neuraminidase inhibitor (NAI) resistance (<1 %) had been detected in circulating viruses. However, there have been reports of significant numbers of A (H1N1) influenza strains with a N294S neuraminidase mutation that was highly resistant to the NAI, oseltamivir. Hence, in the present study, we highlight the effect of point mutation-induced oseltamivir resistance in H1N1 subtype neuraminidases by molecular simulation approach. The docking analysis reveals that mutation (N294S) significantly affects the binding affinity of oseltamivir with mutant type NA. This is mainly due to the decrease in the flexibility of binding site residues and the difference in prevalence of hydrogen bonds in the wild and mutant structures. This study throws light on the possible effects of drug-resistant mutations on the large functionally important collective motions in biological systems.</Para></Abstract><KeywordGroup Language="En" OutputMedium="All"><Heading>Keywords</Heading><Keyword>Neuraminidase</Keyword><Keyword>Oseltamivir resistance</Keyword><Keyword>Molecular docking</Keyword><Keyword>Normal mode analysis</Keyword><Keyword>Molecular dynamic simulation</Keyword></KeywordGroup><ArticleNote Type="CommunicatedBy"><SimplePara>Handling Editor: Peter Nick</SimplePara></ArticleNote></ArticleHeader><NoBody></NoBody></Article></Issue></Volume></Journal></Publisher></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>In silico analysis of drug-resistant mutant of neuraminidase (N294S) against oseltamivir</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>In silico analysis of drug-resistant mutant of neuraminidase (N294S) against oseltamivir</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"><namePart type="given">V.</namePart><namePart type="family">Shanthi</namePart><affiliation>Industrial Biotechnology 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"><namePart type="given">R.</namePart><namePart type="family">Rajasekaran</namePart><affiliation>Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology, 632014, Vellore, Tamil Nadu, India</affiliation><affiliation>E-mail: rrajasekaran@vit.ac.in</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 Vienna</publisher><place><placeTerm type="text">Vienna</placeTerm></place><dateCreated encoding="w3cdtf">2012-01-10</dateCreated><dateIssued encoding="w3cdtf">2013-02-01</dateIssued><copyrightDate encoding="w3cdtf">2012</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><abstract lang="en">Abstract: The recent H1N1 influenza pandemic has attracted worldwide attention due to the high infection rate. Oseltamivir is a new class of anti-viral agent approved for the treatment and prevention of influenza infections. The principal target for this drug is a virus surface glycoprotein, neuraminidase (NA), which facilitates the release of nascent virus and thus spreads infection. Until recently, only a low prevalence of neuraminidase inhibitor (NAI) resistance (<1 %) had been detected in circulating viruses. However, there have been reports of significant numbers of A (H1N1) influenza strains with a N294S neuraminidase mutation that was highly resistant to the NAI, oseltamivir. Hence, in the present study, we highlight the effect of point mutation-induced oseltamivir resistance in H1N1 subtype neuraminidases by molecular simulation approach. The docking analysis reveals that mutation (N294S) significantly affects the binding affinity of oseltamivir with mutant type NA. This is mainly due to the decrease in the flexibility of binding site residues and the difference in prevalence of hydrogen bonds in the wild and mutant structures. This study throws light on the possible effects of drug-resistant mutations on the large functionally important collective motions in biological systems.</abstract><note>Original Article</note><subject lang="en"><genre>Keywords</genre><topic>Neuraminidase</topic><topic>Oseltamivir resistance</topic><topic>Molecular docking</topic><topic>Normal mode analysis</topic><topic>Molecular dynamic simulation</topic></subject><relatedItem type="host"><titleInfo><title>Protoplasma</title><subTitle>An International Journal of Cell Biology</subTitle></titleInfo><titleInfo type="abbreviated"><title>Protoplasma</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">2013-01-29</dateIssued><copyrightDate encoding="w3cdtf">2013</copyrightDate></originInfo><subject><genre>Journal-Subject-Collection</genre><topic authority="SpringerSubjectCodes" authorityURI="SC3">Biomedical and Life Sciences</topic></subject><subject><genre>Journal-Subject-Group</genre><topic authority="SpringerSubjectCodes" authorityURI="SCL">Life Sciences</topic><topic authority="SpringerSubjectCodes" authorityURI="SCL16008">Cell Biology</topic><topic authority="SpringerSubjectCodes" authorityURI="SCL24000">Plant Sciences</topic><topic authority="SpringerSubjectCodes" authorityURI="SCL25007">Zoology</topic></subject><identifier type="ISSN">0033-183X</identifier><identifier type="eISSN">1615-6102</identifier><identifier type="JournalID">709</identifier><identifier type="IssueArticleCount">40</identifier><identifier type="VolumeIssueCount">6</identifier><part><date>2013</date><detail type="volume"><number>250</number><caption>vol.</caption></detail><detail type="issue"><number>1</number><caption>no.</caption></detail><extent unit="pages"><start>197</start><end>207</end></extent></part><recordInfo><recordOrigin>Springer-Verlag Wien, 2013</recordOrigin></recordInfo></relatedItem><identifier type="istex">231846102B7C328F81384CB489C765297DD14409</identifier><identifier type="ark">ark:/67375/VQC-3LDJRL57-9</identifier><identifier type="DOI">10.1007/s00709-012-0394-6</identifier><identifier type="ArticleID">394</identifier><identifier type="ArticleID">s00709-012-0394-6</identifier><accessCondition type="use and reproduction" contentType="copyright">Springer-Verlag, 2012</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>Springer-Verlag, 2012</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-3LDJRL57-9/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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