Synthesis and Biological Evaluation of 2‐oxo‐pyrazine‐3‐carboxamide‐yl Nucleoside Analogues and Their Epimers as Inhibitors of Influenza A Viruses
Identifieur interne : 001061 ( Istex/Corpus ); précédent : 001060; suivant : 001062Synthesis and Biological Evaluation of 2‐oxo‐pyrazine‐3‐carboxamide‐yl Nucleoside Analogues and Their Epimers as Inhibitors of Influenza A Viruses
Auteurs : Jingjing Gao ; Xianjin Luo ; Yuhuan Li ; Rongmei Gao ; Haifeng Chen ; Dingjue JiSource :
- Chemical Biology & Drug Design [ 1747-0277 ] ; 2015-03.
Abstract
Novel 2‐oxo‐pyrazine‐3‐carboxamide‐yl nucleoside analogues and their epimers were designed, synthesized and evaluated for their activities against influenza A viruses H1N1 and H3N2 in Madin‐Darby canine kidney cells. All the compounds showed low cytotoxicities in these anti‐influenza tests. One of the epimers, 4‐[(1S, 3R, 4R, 7R)‐7‐hydroxy‐1‐(hydroxymethyl)‐2,5‐dioxabicyclo[2.2.1]heptan‐3‐yl]‐3‐oxo‐3,4‐dihydropyrazine‐2‐carboxamide 8a, with high antiviral activities (IC50 = 7.41, 5.63 μm for H3N2 and H1N1, respectively) and remarkable low cytotoxicity (TC50 > 200 μm), has great potential for further development as a novel anti‐influenza A agent. Molecular docking of compound 8a with RNA‐dependent RNA polymerase was performed to understand the binding mode between these inhibitors and the active site of RdRp and to rationalize some SARs.
Novel 2‐oxo‐pyrazine‐3‐carboxamide‐yl nucleoside analogues and their epimers were designed, synthesized, and evaluated for their activities against influenza A viruses H1N1 and H3N2 in MDCK cells. All the compounds showed low cytotoxicities in these anti‐influenza tests. One of the epimers 8a shows high antiviral activity (IC50 = 7.41, 5.63 μm for H3N2 and H1N1, respectively) and remarkable low cytotoxicity (TC50 > 200 μm). Molecular docking of compound 8a with RNA‐dependent RNA polymerase was performed to understand the binding mode between these inhibitors and the active site of RdRp.
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DOI: 10.1111/cbdd.12382
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Gao</name><affiliation><mods:affiliation>School of Chemistry and Chemical Engineering, Shanghai JiaoTong University, 200240, Shanghai, China</mods:affiliation></affiliation></author><author><name sortKey="Luo, Xianjin" sort="Luo, Xianjin" uniqKey="Luo X" first="Xianjin" last="Luo">Xianjin Luo</name><affiliation><mods:affiliation>School of Chemistry and Chemical Engineering, Shanghai JiaoTong University, 200240, Shanghai, China</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: luoxianjin@sjtu.edu.cn</mods:affiliation></affiliation></author><author><name sortKey="Li, Yuhuan" sort="Li, Yuhuan" uniqKey="Li Y" first="Yuhuan" last="Li">Yuhuan Li</name><affiliation><mods:affiliation>Institute of Medical Biotechnology, Chinese Academy of Medical Science, 100050, Beijing, China</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: luoxianjin@sjtu.edu.cn</mods:affiliation></affiliation></author><author><name sortKey="Gao, Rongmei" sort="Gao, Rongmei" 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All the compounds showed low cytotoxicities in these anti‐influenza tests. One of the epimers, 4‐[(1S, 3R, 4R, 7R)‐7‐hydroxy‐1‐(hydroxymethyl)‐2,5‐dioxabicyclo[2.2.1]heptan‐3‐yl]‐3‐oxo‐3,4‐dihydropyrazine‐2‐carboxamide 8a, with high antiviral activities (IC50 = 7.41, 5.63 μm for H3N2 and H1N1, respectively) and remarkable low cytotoxicity (TC50 > 200 μm), has great potential for further development as a novel anti‐influenza A agent. Molecular docking of compound 8a with RNA‐dependent RNA polymerase was performed to understand the binding mode between these inhibitors and the active site of RdRp and to rationalize some SARs.</div><div type="abstract">Novel 2‐oxo‐pyrazine‐3‐carboxamide‐yl nucleoside analogues and their epimers were designed, synthesized, and evaluated for their activities against influenza A viruses H1N1 and H3N2 in MDCK cells. All the compounds showed low cytotoxicities in these anti‐influenza tests. One of the epimers 8a shows high antiviral activity (IC50 = 7.41, 5.63 μm for H3N2 and H1N1, respectively) and remarkable low cytotoxicity (TC50 > 200 μm). Molecular docking of compound 8a with RNA‐dependent RNA polymerase was performed to understand the binding mode between these inhibitors and the active site of RdRp.</div></front></TEI><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>nucleoside</json:string><json:string>chem</json:string><json:string>calcd</json:string><json:string>white solid</json:string><json:string>anal</json:string><json:string>mmol</json:string><json:string>furuta</json:string><json:string>biol</json:string><json:string>reflux</json:string><json:string>cytotoxicity</json:string><json:string>antiviral</json:string><json:string>analogue</json:string><json:string>chem biol drug</json:string><json:string>general procedure</json:string><json:string>influenza</json:string><json:string>column chromatography</json:string><json:string>nucleoside analogue</json:string><json:string>nucleic acid</json:string><json:string>influenza virus</json:string><json:string>antimicrob agent</json:string><json:string>nucleic</json:string><json:string>mdck cell</json:string><json:string>target compound</json:string><json:string>binding mode</json:string><json:string>inhibitor</json:string><json:string>ambient temperature</json:string><json:string>pyrazinecarboxamide derivative</json:string><json:string>aqueous solution</json:string><json:string>epimer bicyclic nucleoside</json:string><json:string>chemical structure</json:string><json:string>hamster model</json:string><json:string>methanolic ammonia</json:string><json:string>reaction mixture</json:string><json:string>catalytical amount</json:string><json:string>hydrogen atmosphere</json:string><json:string>solid residue</json:string><json:string>cell well</json:string><json:string>virus well</json:string><json:string>virus growth</json:string><json:string>maximum number</json:string><json:string>novel nucleoside analogue</json:string><json:string>pentofuranose derivative</json:string><json:string>active site</json:string><json:string>4hydroxymethyl group</json:string><json:string>hydroxyl group</json:string><json:string>hydrogen bond</json:string><json:string>potent activity</json:string><json:string>antiviral activity</json:string><json:string>shanghai jiaotong university</json:string><json:string>anhydrous acetonitrile</json:string><json:string>yellow fever virus infection</json:string><json:string>dryness</json:string></teeft></keywords><author><json:item><name>Jingjing Gao</name><affiliations><json:string>School of Chemistry and Chemical Engineering, Shanghai JiaoTong University, 200240, Shanghai, China</json:string></affiliations></json:item><json:item><name>Xianjin Luo</name><affiliations><json:string>School of Chemistry and Chemical Engineering, Shanghai JiaoTong University, 200240, Shanghai, China</json:string><json:string>E-mail: luoxianjin@sjtu.edu.cn</json:string></affiliations></json:item><json:item><name>Yuhuan Li</name><affiliations><json:string>Institute of Medical Biotechnology, Chinese Academy of Medical Science, 100050, Beijing, China</json:string><json:string>E-mail: luoxianjin@sjtu.edu.cn</json:string></affiliations></json:item><json:item><name>Rongmei Gao</name><affiliations><json:string>Institute of Medical Biotechnology, Chinese Academy of Medical Science, 100050, Beijing, China</json:string></affiliations></json:item><json:item><name>Haifeng Chen</name><affiliations><json:string>School of Life Sciences and Biotechnology, Shanghai JiaoTong University, 200240, Shanghai, China</json:string></affiliations></json:item><json:item><name>Dingjue Ji</name><affiliations><json:string>School of Life Sciences and Biotechnology, Shanghai JiaoTong University, 200240, Shanghai, China</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>binding mode</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>influenza A H1N1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>influenza A H3N2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>nucleoside analogues</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>pyrazinecarboxamide derivatives</value></json:item></subject><articleId><json:string>CBDD12382</json:string></articleId><arkIstex>ark:/67375/WNG-FG2JN3LB-M</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>editorial</json:string></originalGenre><abstract>Novel 2‐oxo‐pyrazine‐3‐carboxamide‐yl nucleoside analogues and their epimers were designed, synthesized and evaluated for their activities against influenza A viruses H1N1 and H3N2 in Madin‐Darby canine kidney cells. 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<ref target="http://www.tei-c.org/">We use TEI</ref></desc></application></appInfo></encodingDesc><profileDesc><abstract style="main" xml:id="cbdd12382-abs-0001"><p>Novel 2‐oxo‐pyrazine‐3‐carboxamide‐yl nucleoside analogues and their epimers were designed, synthesized and evaluated for their activities against influenza A viruses H1N1 and H3N2 in <hi rend="fc">Madin‐Darby canine kidney</hi> cells. All the compounds showed low cytotoxicities in these anti‐influenza tests. One of the epimers, 4‐[(1S, 3R, 4R, 7R)‐7‐hydroxy‐1‐(hydroxymethyl)‐2,5‐dioxabicyclo[2.2.1]heptan‐3‐yl]‐3‐oxo‐3,4‐dihydropyrazine‐2‐carboxamide <hi rend="bold">8</hi>a, with high antiviral activities (<hi rend="fc">IC</hi><hi rend="subscript">50</hi> = 7.41, 5.63 <hi rend="italic">μ</hi><hi rend="smallCaps">m</hi> for H3N2 and H1N1, respectively) and remarkable low cytotoxicity (<hi rend="fc">TC</hi><hi rend="subscript">50</hi> > 200 <hi rend="italic">μ</hi><hi rend="smallCaps">m</hi>), has great potential for further development as a novel anti‐influenza A agent. Molecular docking of compound <hi rend="bold">8a</hi> with <hi rend="fc">RNA</hi>‐dependent <hi rend="fc">RNA</hi> polymerase was performed to understand the binding mode between these inhibitors and the active site of RdRp and to rationalize some <hi rend="fc">SAR</hi>s.</p></abstract><abstract style="graphical" xml:id="cbdd12382-abs-0002"><p>Novel 2‐oxo‐pyrazine‐3‐carboxamide‐yl nucleoside analogues and their epimers were designed, synthesized, and evaluated for their activities against influenza A viruses H1N1 and H3N2 in <hi rend="fc">MDCK</hi> cells. All the compounds showed low cytotoxicities in these anti‐influenza tests. One of the epimers <hi rend="bold">8a</hi> shows high antiviral activity (<hi rend="fc">IC</hi><hi rend="subscript">50</hi> = 7.41, 5.63 <hi rend="italic">μ</hi><hi rend="smallCaps">m</hi> for H3N2 and H1N1, respectively) and remarkable low cytotoxicity (<hi rend="fc">TC</hi><hi rend="subscript">50</hi> > 200 <hi rend="italic">μ</hi><hi rend="smallCaps">m</hi>). Molecular docking of compound <hi rend="bold">8a</hi> with <hi rend="fc">RNA</hi>‐dependent <hi rend="fc">RNA</hi> polymerase was performed to understand the binding mode between these inhibitors and the active site of RdRp.
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position="30"><doi origin="wiley">10.1111/cbdd.2015.85.issue-3</doi><copyright ownership="publisher">Copyright © 2015 John Wiley & Sons A/S</copyright><numberingGroup><numbering type="journalVolume" number="85">85</numbering><numbering type="journalIssue">3</numbering></numberingGroup><coverDate startDate="2015-03">March 2015</coverDate></publicationMeta><publicationMeta level="unit" position="20" status="forIssue" type="editorial"><doi>10.1111/cbdd.12382</doi><idGroup><id type="unit" value="CBDD12382"></id></idGroup><countGroup><count number="8" type="pageTotal"></count></countGroup><titleGroup><title type="articleCategory">Editor's Choice</title><title type="tocHeading1">Editor's Choice</title></titleGroup><copyright ownership="publisher">© 2014 John Wiley & Sons A/S</copyright><eventGroup><event date="2014-04-01" type="manuscriptReceived"></event><event date="2014-05-22" type="manuscriptRevised"></event><event date="2014-06-12" type="manuscriptAccepted"></event><event agent="SPS" date="2014-06-20" type="xmlCreated"></event><event type="publishedOnlineAccepted" date="2014-06-20"></event><event type="publishedOnlineEarlyUnpaginated" date="2014-07-12"></event><event type="firstOnline" date="2014-07-12"></event><event type="publishedOnlineFinalForm" date="2015-02-12"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.7.2 mode:FullText" date="2016-01-04"></event></eventGroup><numberingGroup><numbering type="pageFirst">245</numbering><numbering type="pageLast">252</numbering></numberingGroup><correspondenceTo>Corresponding authors: Xianjin Luo, <email>luoxianjin@sjtu.edu.cn</email> <i>and Yuhuan Li,</i> <email>yuhuanlibj@126.com</email></correspondenceTo><objectNameGroup><objectName elementName="figure">Scheme</objectName></objectNameGroup><linkGroup><link type="toTypesetVersion" href="file:CBDD.CBDD12382.pdf"></link></linkGroup></publicationMeta><contentMeta><titleGroup><title type="main">Synthesis and Biological Evaluation of 2‐oxo‐pyrazine‐3‐carboxamide‐yl Nucleoside Analogues and Their Epimers as Inhibitors of Influenza A Viruses</title><title type="shortAuthors">Gao et al.</title></titleGroup><creators><creator affiliationRef="#cbdd12382-aff-0001" creatorRole="author" xml:id="cbdd12382-cr-0001"><personName><givenNames>Jingjing</givenNames> <familyName>Gao</familyName></personName></creator><creator affiliationRef="#cbdd12382-aff-0001" corresponding="yes" creatorRole="author" xml:id="cbdd12382-cr-0002"><personName><givenNames>Xianjin</givenNames> <familyName>Luo</familyName></personName></creator><creator affiliationRef="#cbdd12382-aff-0002" corresponding="yes" creatorRole="author" xml:id="cbdd12382-cr-0003"><personName><givenNames>Yuhuan</givenNames> <familyName>Li</familyName></personName></creator><creator affiliationRef="#cbdd12382-aff-0002" creatorRole="author" xml:id="cbdd12382-cr-0004"><personName><givenNames>Rongmei</givenNames> <familyName>Gao</familyName></personName></creator><creator affiliationRef="#cbdd12382-aff-0003" creatorRole="author" xml:id="cbdd12382-cr-0005"><personName><givenNames>Haifeng</givenNames> <familyName>Chen</familyName></personName></creator><creator affiliationRef="#cbdd12382-aff-0003" creatorRole="author" xml:id="cbdd12382-cr-0006"><personName><givenNames>Dingjue</givenNames> <familyName>Ji</familyName></personName></creator></creators><affiliationGroup><affiliation countryCode="CN" type="organization" xml:id="cbdd12382-aff-0001"><orgDiv>School of Chemistry and Chemical Engineering</orgDiv> <orgName>Shanghai JiaoTong University</orgName> <address><city>Shanghai</city> <postCode>200240</postCode> <country>China</country></address></affiliation><affiliation countryCode="CN" type="organization" xml:id="cbdd12382-aff-0002"><orgDiv>Institute of Medical Biotechnology</orgDiv> <orgName>Chinese Academy of Medical Science</orgName> <address><city>Beijing</city> <postCode>100050</postCode> <country>China</country></address></affiliation><affiliation countryCode="CN" type="organization" xml:id="cbdd12382-aff-0003"><orgDiv>School of Life Sciences and Biotechnology</orgDiv> <orgName>Shanghai JiaoTong University</orgName> <address><city>Shanghai</city> <postCode>200240</postCode> <country>China</country></address></affiliation></affiliationGroup><keywordGroup type="author"><keyword xml:id="cbdd12382-kwd-0001">binding mode</keyword><keyword xml:id="cbdd12382-kwd-0002">influenza A H1N1</keyword><keyword xml:id="cbdd12382-kwd-0003">influenza A H3N2</keyword><keyword xml:id="cbdd12382-kwd-0004">nucleoside analogues</keyword><keyword xml:id="cbdd12382-kwd-0005">pyrazinecarboxamide derivatives</keyword></keywordGroup><abstractGroup><abstract type="main" xml:id="cbdd12382-abs-0001"><p>Novel 2‐oxo‐pyrazine‐3‐carboxamide‐yl nucleoside analogues and their epimers were designed, synthesized and evaluated for their activities against influenza A viruses H1N1 and H3N2 in <fc>Madin‐Darby canine kidney</fc> cells. All the compounds showed low cytotoxicities in these anti‐influenza tests. One of the epimers, 4‐[(1S, 3R, 4R, 7R)‐7‐hydroxy‐1‐(hydroxymethyl)‐2,5‐dioxabicyclo[2.2.1]heptan‐3‐yl]‐3‐oxo‐3,4‐dihydropyrazine‐2‐carboxamide <b>8</b>a, with high antiviral activities (<fc>IC</fc><sub>50</sub> = 7.41, 5.63 <i>μ</i><sc>m</sc> for H3N2 and H1N1, respectively) and remarkable low cytotoxicity (<fc>TC</fc><sub>50</sub> > 200 <i>μ</i><sc>m</sc>), has great potential for further development as a novel anti‐influenza A agent. Molecular docking of compound <b>8a</b> with <fc>RNA</fc>‐dependent <fc>RNA</fc> polymerase was performed to understand the binding mode between these inhibitors and the active site of RdRp and to rationalize some <fc>SAR</fc>s.</p></abstract><abstract type="graphical" xml:id="cbdd12382-abs-0002"><p>Novel 2‐oxo‐pyrazine‐3‐carboxamide‐yl nucleoside analogues and their epimers were designed, synthesized, and evaluated for their activities against influenza A viruses H1N1 and H3N2 in <fc>MDCK</fc> cells. All the compounds showed low cytotoxicities in these anti‐influenza tests. One of the epimers <b>8a</b> shows high antiviral activity (<fc>IC</fc><sub>50</sub> = 7.41, 5.63 <i>μ</i><sc>m</sc> for H3N2 and H1N1, respectively) and remarkable low cytotoxicity (<fc>TC</fc><sub>50</sub> > 200 <i>μ</i><sc>m</sc>). Molecular docking of compound <b>8a</b> with <fc>RNA</fc>‐dependent <fc>RNA</fc> polymerase was performed to understand the binding mode between these inhibitors and the active site of RdRp.
<blockFixed type="graphic" xml:id="cbdd12382-blkfxd-0001"><mediaResourceGroup><mediaResource alt="image" href="urn:x-wiley:17470277:cbdd12382:cbdd12382-toc-0001"></mediaResource></mediaResourceGroup></blockFixed></p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Synthesis and Biological Evaluation of 2‐oxo‐pyrazine‐3‐carboxamide‐yl Nucleoside Analogues and Their Epimers as Inhibitors of Influenza A Viruses</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Synthesis and Biological Evaluation of 2‐oxo‐pyrazine‐3‐carboxamide‐yl Nucleoside Analogues and Their Epimers as Inhibitors of Influenza A Viruses</title></titleInfo><name type="personal"><namePart type="given">Jingjing</namePart><namePart type="family">Gao</namePart><affiliation>School of Chemistry and Chemical Engineering, Shanghai JiaoTong University, 200240, Shanghai, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Xianjin</namePart><namePart type="family">Luo</namePart><affiliation>School of Chemistry and Chemical Engineering, Shanghai JiaoTong University, 200240, Shanghai, China</affiliation><affiliation>E-mail: luoxianjin@sjtu.edu.cn</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yuhuan</namePart><namePart type="family">Li</namePart><affiliation>Institute of Medical Biotechnology, Chinese Academy of Medical Science, 100050, Beijing, China</affiliation><affiliation>E-mail: luoxianjin@sjtu.edu.cn</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rongmei</namePart><namePart type="family">Gao</namePart><affiliation>Institute of Medical Biotechnology, Chinese Academy of Medical Science, 100050, Beijing, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Haifeng</namePart><namePart type="family">Chen</namePart><affiliation>School of Life Sciences and Biotechnology, Shanghai JiaoTong University, 200240, Shanghai, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dingjue</namePart><namePart type="family">Ji</namePart><affiliation>School of Life Sciences and Biotechnology, Shanghai JiaoTong University, 200240, Shanghai, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="editorial" displayLabel="editorial" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-STW636XV-K">editorial</genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><dateIssued encoding="w3cdtf">2015-03</dateIssued><dateCreated encoding="w3cdtf">2014-06-20</dateCreated><dateCaptured encoding="w3cdtf">2014-04-01</dateCaptured><dateValid encoding="w3cdtf">2014-06-12</dateValid><copyrightDate encoding="w3cdtf">2015</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><abstract>Novel 2‐oxo‐pyrazine‐3‐carboxamide‐yl nucleoside analogues and their epimers were designed, synthesized and evaluated for their activities against influenza A viruses H1N1 and H3N2 in Madin‐Darby canine kidney cells. All the compounds showed low cytotoxicities in these anti‐influenza tests. One of the epimers, 4‐[(1S, 3R, 4R, 7R)‐7‐hydroxy‐1‐(hydroxymethyl)‐2,5‐dioxabicyclo[2.2.1]heptan‐3‐yl]‐3‐oxo‐3,4‐dihydropyrazine‐2‐carboxamide 8a, with high antiviral activities (IC50 = 7.41, 5.63 μm for H3N2 and H1N1, respectively) and remarkable low cytotoxicity (TC50 > 200 μm), has great potential for further development as a novel anti‐influenza A agent. Molecular docking of compound 8a with RNA‐dependent RNA polymerase was performed to understand the binding mode between these inhibitors and the active site of RdRp and to rationalize some SARs.</abstract><abstract type="graphical">Novel 2‐oxo‐pyrazine‐3‐carboxamide‐yl nucleoside analogues and their epimers were designed, synthesized, and evaluated for their activities against influenza A viruses H1N1 and H3N2 in MDCK cells. All the compounds showed low cytotoxicities in these anti‐influenza tests. One of the epimers 8a shows high antiviral activity (IC50 = 7.41, 5.63 μm for H3N2 and H1N1, respectively) and remarkable low cytotoxicity (TC50 > 200 μm). Molecular docking of compound 8a with RNA‐dependent RNA polymerase was performed to understand the binding mode between these inhibitors and the active site of RdRp.</abstract><subject><genre>keywords</genre><topic>binding mode</topic><topic>influenza A H1N1</topic><topic>influenza A H3N2</topic><topic>nucleoside analogues</topic><topic>pyrazinecarboxamide derivatives</topic></subject><relatedItem type="host"><titleInfo><title>Chemical Biology & Drug Design</title></titleInfo><titleInfo type="abbreviated"><title>Chem Biol Drug Des</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><subject><genre>article-category</genre><topic>Editor's Choice</topic><topic>Editor's Choice</topic></subject><identifier type="ISSN">1747-0277</identifier><identifier type="eISSN">1747-0285</identifier><identifier type="DOI">10.1111/(ISSN)1747-0285</identifier><identifier type="PublisherID">CBDD</identifier><part><date>2015</date><detail type="volume"><caption>vol.</caption><number>85</number></detail><detail type="issue"><caption>no.</caption><number>3</number></detail><extent unit="pages"><start>245</start><end>252</end><total>8</total></extent></part></relatedItem><relatedItem type="references" displayLabel="cbdd12382-cit-0001"><titleInfo><title>The evolution of influenza resistance and treatment</title></titleInfo><name type="personal"><namePart type="given">D.M.</namePart><namePart type="family">Weinstock</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G.</namePart><namePart type="family">Zuccotti</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Weinstock D.M., Zuccotti G. 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