De Novo Design of α-Helical Lipopeptides Targeting Viral Fusion Proteins: A Promising Strategy for Relatively Broad-Spectrum Antiviral Drug Discovery
Identifieur interne : 000605 ( Pmc/Checkpoint ); précédent : 000604; suivant : 000606De Novo Design of α-Helical Lipopeptides Targeting Viral Fusion Proteins: A Promising Strategy for Relatively Broad-Spectrum Antiviral Drug Discovery
Auteurs : Chao Wang [République populaire de Chine] ; Lei Zhao [République populaire de Chine] ; Shuai Xia [République populaire de Chine] ; Tianhong Zhang [République populaire de Chine] ; Ruiyuan Cao [République populaire de Chine] ; Guodong Liang [République populaire de Chine] ; Yue Li [République populaire de Chine] ; Guangpeng Meng [République populaire de Chine] ; Weicong Wang [République populaire de Chine] ; Weiguo Shi [République populaire de Chine] ; Wu Zhong [République populaire de Chine] ; Shibo Jiang [République populaire de Chine, États-Unis] ; Keliang Liu [République populaire de Chine]Source :
- Journal of Medicinal Chemistry [ 0022-2623 ] ; 2018.
Abstract
Class I enveloped viruses share similarities in their apparent use of a hexameric coiled-coil assembly to drive the merging of virus and host cell membranes. Inhibition of coiled coil-mediated interactions using bioactive peptides that replicate an α-helical chain from the viral fusion machinery has significant antiviral potential. Here, we present the construction of a series of lipopeptides composed of a de novo heptad repeat sequence-based α-helical peptide plus a hydrocarbon tail. Promisingly, the constructs adopted stable α-helical conformations and exhibited relatively broad-spectrum antiviral activities against Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza A viruses (IAVs). Together, these findings reveal a new strategy for relatively broad-spectrum antiviral drug discovery by relying on the tunability of the α-helical coiled-coil domains present in all class I fusion proteins and the amphiphilic nature of the individual helices from this multihelix motif.
Url:
DOI: 10.1021/acs.jmedchem.8b00890
PubMed: 30192544
PubMed Central: 7075651
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">De Novo Design
of α-Helical Lipopeptides
Targeting Viral Fusion Proteins: A Promising Strategy for Relatively
Broad-Spectrum Antiviral Drug Discovery</title><author><name sortKey="Wang, Chao" sort="Wang, Chao" uniqKey="Wang C" first="Chao" last="Wang">Chao Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhao, Lei" sort="Zhao, Lei" uniqKey="Zhao L" first="Lei" last="Zhao">Lei Zhao</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Xia, Shuai" sort="Xia, Shuai" uniqKey="Xia S" first="Shuai" last="Xia">Shuai Xia</name><affiliation wicri:level="1"><nlm:aff id="aff2">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences & Shanghai Public Health Clinical Center,<institution>Fudan University</institution>, 130 Dong An Road, Shanghai 200032,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Tianhong" sort="Zhang, Tianhong" uniqKey="Zhang T" first="Tianhong" last="Zhang">Tianhong Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cao, Ruiyuan" sort="Cao, Ruiyuan" uniqKey="Cao R" first="Ruiyuan" last="Cao">Ruiyuan Cao</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liang, Guodong" sort="Liang, Guodong" uniqKey="Liang G" first="Guodong" last="Liang">Guodong Liang</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Li, Yue" sort="Li, Yue" uniqKey="Li Y" first="Yue" last="Li">Yue Li</name><affiliation wicri:level="1"><nlm:aff id="aff3">Key Laboratory of Structure-Based Drug Design & Discovery of the Ministry of Education,<institution>Shenyang Pharmaceutical University</institution>, Shenyang 110016,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Meng, Guangpeng" sort="Meng, Guangpeng" uniqKey="Meng G" first="Guangpeng" last="Meng">Guangpeng Meng</name><affiliation wicri:level="1"><nlm:aff id="aff3">Key Laboratory of Structure-Based Drug Design & Discovery of the Ministry of Education,<institution>Shenyang Pharmaceutical University</institution>, Shenyang 110016,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Weicong" sort="Wang, Weicong" uniqKey="Wang W" first="Weicong" last="Wang">Weicong Wang</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Clinical Trial Center, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital,<institution>Capital Medical University</institution>, Beijing 100050,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shi, Weiguo" sort="Shi, Weiguo" uniqKey="Shi W" first="Weiguo" last="Shi">Weiguo Shi</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhong, Wu" sort="Zhong, Wu" uniqKey="Zhong W" first="Wu" last="Zhong">Wu Zhong</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><affiliation wicri:level="1"><nlm:aff id="aff2">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences & Shanghai Public Health Clinical Center,<institution>Fudan University</institution>, 130 Dong An Road, Shanghai 200032,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Lindsley F. Kimball Research Institute,<institution>New York Blood Center</institution>, New York, New York 10065,<country>United States</country>;</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Keliang" sort="Liu, Keliang" uniqKey="Liu K" first="Keliang" last="Liu">Keliang Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">30192544</idno><idno type="pmc">7075651</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075651</idno><idno type="RBID">PMC:7075651</idno><idno type="doi">10.1021/acs.jmedchem.8b00890</idno><date when="2018">2018</date><idno type="wicri:Area/Pmc/Corpus">000131</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000131</idno><idno type="wicri:Area/Pmc/Curation">000131</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000131</idno><idno type="wicri:Area/Pmc/Checkpoint">000605</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000605</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">De Novo Design
of α-Helical Lipopeptides
Targeting Viral Fusion Proteins: A Promising Strategy for Relatively
Broad-Spectrum Antiviral Drug Discovery</title><author><name sortKey="Wang, Chao" sort="Wang, Chao" uniqKey="Wang C" first="Chao" last="Wang">Chao Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhao, Lei" sort="Zhao, Lei" uniqKey="Zhao L" first="Lei" last="Zhao">Lei Zhao</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Xia, Shuai" sort="Xia, Shuai" uniqKey="Xia S" first="Shuai" last="Xia">Shuai Xia</name><affiliation wicri:level="1"><nlm:aff id="aff2">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences & Shanghai Public Health Clinical Center,<institution>Fudan University</institution>, 130 Dong An Road, Shanghai 200032,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Tianhong" sort="Zhang, Tianhong" uniqKey="Zhang T" first="Tianhong" last="Zhang">Tianhong Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cao, Ruiyuan" sort="Cao, Ruiyuan" uniqKey="Cao R" first="Ruiyuan" last="Cao">Ruiyuan Cao</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liang, Guodong" sort="Liang, Guodong" uniqKey="Liang G" first="Guodong" last="Liang">Guodong Liang</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Li, Yue" sort="Li, Yue" uniqKey="Li Y" first="Yue" last="Li">Yue Li</name><affiliation wicri:level="1"><nlm:aff id="aff3">Key Laboratory of Structure-Based Drug Design & Discovery of the Ministry of Education,<institution>Shenyang Pharmaceutical University</institution>, Shenyang 110016,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Meng, Guangpeng" sort="Meng, Guangpeng" uniqKey="Meng G" first="Guangpeng" last="Meng">Guangpeng Meng</name><affiliation wicri:level="1"><nlm:aff id="aff3">Key Laboratory of Structure-Based Drug Design & Discovery of the Ministry of Education,<institution>Shenyang Pharmaceutical University</institution>, Shenyang 110016,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Weicong" sort="Wang, Weicong" uniqKey="Wang W" first="Weicong" last="Wang">Weicong Wang</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Clinical Trial Center, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital,<institution>Capital Medical University</institution>, Beijing 100050,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shi, Weiguo" sort="Shi, Weiguo" uniqKey="Shi W" first="Weiguo" last="Shi">Weiguo Shi</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhong, Wu" sort="Zhong, Wu" uniqKey="Zhong W" first="Wu" last="Zhong">Wu Zhong</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><affiliation wicri:level="1"><nlm:aff id="aff2">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences & Shanghai Public Health Clinical Center,<institution>Fudan University</institution>, 130 Dong An Road, Shanghai 200032,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Lindsley F. Kimball Research Institute,<institution>New York Blood Center</institution>, New York, New York 10065,<country>United States</country>;</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Keliang" sort="Liu, Keliang" uniqKey="Liu K" first="Keliang" last="Liu">Keliang Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Journal of Medicinal Chemistry</title><idno type="ISSN">0022-2623</idno><idno type="eISSN">1520-4804</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p content-type="toc-graphic"><graphic xlink:href="jm8b00890_0008" id="ab-tgr1"></graphic></p><p>Class I enveloped viruses share similarities
in their apparent
use of a hexameric coiled-coil assembly to drive the merging of virus
and host cell membranes. Inhibition of coiled coil-mediated interactions
using bioactive peptides that replicate an α-helical chain from
the viral fusion machinery has significant antiviral potential. Here,
we present the construction of a series of lipopeptides composed of
a de novo heptad repeat sequence-based α-helical peptide plus
a hydrocarbon tail. Promisingly, the constructs adopted stable α-helical
conformations and exhibited relatively broad-spectrum antiviral activities
against Middle East respiratory syndrome coronavirus (MERS-CoV) and
influenza A viruses (IAVs). Together, these findings reveal a new
strategy for relatively broad-spectrum antiviral drug discovery by
relying on the tunability of the α-helical coiled-coil domains
present in all class I fusion proteins and the amphiphilic nature
of the individual helices from this multihelix motif.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="De X0a Clercq, E" uniqKey="De X0a Clercq E">E. De
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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Med Chem</journal-id><journal-id journal-id-type="iso-abbrev">J. Med. Chem</journal-id><journal-id journal-id-type="publisher-id">jm</journal-id><journal-id journal-id-type="coden">jmcmar</journal-id><journal-title-group><journal-title>Journal of Medicinal Chemistry</journal-title></journal-title-group><issn pub-type="ppub">0022-2623</issn><issn pub-type="epub">1520-4804</issn><publisher><publisher-name>American Chemical
Society</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">30192544</article-id><article-id pub-id-type="pmc">7075651</article-id><article-id pub-id-type="doi">10.1021/acs.jmedchem.8b00890</article-id><article-categories><subj-group><subject>Article</subject></subj-group></article-categories><title-group><article-title>De Novo Design
of α-Helical Lipopeptides
Targeting Viral Fusion Proteins: A Promising Strategy for Relatively
Broad-Spectrum Antiviral Drug Discovery</article-title></title-group><contrib-group><contrib contrib-type="author" id="ath1"><name><surname>Wang</surname><given-names>Chao</given-names></name><xref rid="aff1" ref-type="aff">†</xref><xref rid="notes3" ref-type="notes">¶</xref></contrib><contrib contrib-type="author" id="ath2"><name><surname>Zhao</surname><given-names>Lei</given-names></name><xref rid="aff1" ref-type="aff">†</xref><xref rid="notes3" ref-type="notes">¶</xref></contrib><contrib contrib-type="author" id="ath3"><name><surname>Xia</surname><given-names>Shuai</given-names></name><xref rid="aff2" ref-type="aff">‡</xref><xref rid="notes3" ref-type="notes">¶</xref></contrib><contrib contrib-type="author" id="ath4"><name><surname>Zhang</surname><given-names>Tianhong</given-names></name><xref rid="aff1" ref-type="aff">†</xref><xref rid="notes3" ref-type="notes">¶</xref></contrib><contrib contrib-type="author" id="ath5"><name><surname>Cao</surname><given-names>Ruiyuan</given-names></name><xref rid="aff1" ref-type="aff">†</xref></contrib><contrib contrib-type="author" id="ath6"><name><surname>Liang</surname><given-names>Guodong</given-names></name><xref rid="aff1" ref-type="aff">†</xref></contrib><contrib contrib-type="author" id="ath7"><name><surname>Li</surname><given-names>Yue</given-names></name><xref rid="aff3" ref-type="aff">#</xref></contrib><contrib contrib-type="author" id="ath8"><name><surname>Meng</surname><given-names>Guangpeng</given-names></name><xref rid="aff3" ref-type="aff">#</xref></contrib><contrib contrib-type="author" id="ath9"><name><surname>Wang</surname><given-names>Weicong</given-names></name><xref rid="aff5" ref-type="aff">∥</xref></contrib><contrib contrib-type="author" id="ath10"><name><surname>Shi</surname><given-names>Weiguo</given-names></name><xref rid="aff1" ref-type="aff">†</xref></contrib><contrib contrib-type="author" corresp="yes" id="ath11"><name><surname>Zhong</surname><given-names>Wu</given-names></name><xref rid="cor3" ref-type="other">*</xref><xref rid="aff1" ref-type="aff">†</xref></contrib><contrib contrib-type="author" corresp="yes" id="ath12"><name><surname>Jiang</surname><given-names>Shibo</given-names></name><xref rid="cor2" ref-type="other">*</xref><xref rid="aff2" ref-type="aff">‡</xref><xref rid="aff4" ref-type="aff">§</xref></contrib><contrib contrib-type="author" corresp="yes" id="ath13"><name><surname>Liu</surname><given-names>Keliang</given-names></name><xref rid="cor1" ref-type="other">*</xref><xref rid="aff1" ref-type="aff">†</xref></contrib><aff id="aff1"><label>†</label>State Key Laboratory of Toxicology and Medical Countermeasures,<institution>Beijing Institute of Pharmacology and Toxicology</institution>, 27 Tai-Ping Road, Beijing 100850,<country>China</country></aff><aff id="aff2"><label>‡</label>Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences & Shanghai Public Health Clinical Center,<institution>Fudan University</institution>, 130 Dong An Road, Shanghai 200032,<country>China</country></aff><aff id="aff3"><label>#</label>Key Laboratory of Structure-Based Drug Design & Discovery of the Ministry of Education,<institution>Shenyang Pharmaceutical University</institution>, Shenyang 110016,<country>China</country></aff><aff id="aff4"><label>§</label>Lindsley F. Kimball Research Institute,<institution>New York Blood Center</institution>, New York, New York 10065,<country>United States</country>;</aff><aff id="aff5"><label>∥</label>Department of Clinical Trial Center, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital,<institution>Capital Medical University</institution>, Beijing 100050,<country>China</country></aff></contrib-group><author-notes><corresp id="cor1"><label>*</label>For
K.L.: phone, <phone>86-10-6816-9363</phone>; fax, <fax>86-10-6821-1656</fax>; E-mail, <email>keliangliu55@126.com</email>.</corresp><corresp id="cor2"><label>*</label>For S.J.: phone, <phone>86-21-54237673</phone>; fax, <fax>86-21-54237465</fax>; E-mail, <email>shibojiang@fudan.edu.cn</email>.</corresp><corresp id="cor3"><label>*</label>For W.Z.: phone, <phone>86-10-6816-9363</phone>; fax, <fax>86-10-6821-1656</fax>, E-mail, <email>zhongwu@bmi.ac.cn</email>.</corresp></author-notes><pub-date pub-type="epub"><day>07</day><month>09</month><year>2018</year></pub-date><pub-date pub-type="ppub"><day>11</day><month>10</month><year>2018</year></pub-date><volume>61</volume><issue>19</issue><fpage>8734</fpage><lpage>8745</lpage><history><date date-type="received"><day>05</day><month>06</month><year>2018</year></date></history><permissions><copyright-statement>Copyright © 2018 American Chemical
Society</copyright-statement><copyright-year>2018</copyright-year><copyright-holder>American Chemical
Society</copyright-holder><license license-type="open-access"><license-p>This article is made available via the PMC Open Access Subset for unrestricted RESEARCH re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.</license-p></license></permissions><abstract><p content-type="toc-graphic"><graphic xlink:href="jm8b00890_0008" id="ab-tgr1"></graphic></p><p>Class I enveloped viruses share similarities
in their apparent
use of a hexameric coiled-coil assembly to drive the merging of virus
and host cell membranes. Inhibition of coiled coil-mediated interactions
using bioactive peptides that replicate an α-helical chain from
the viral fusion machinery has significant antiviral potential. Here,
we present the construction of a series of lipopeptides composed of
a de novo heptad repeat sequence-based α-helical peptide plus
a hydrocarbon tail. Promisingly, the constructs adopted stable α-helical
conformations and exhibited relatively broad-spectrum antiviral activities
against Middle East respiratory syndrome coronavirus (MERS-CoV) and
influenza A viruses (IAVs). Together, these findings reveal a new
strategy for relatively broad-spectrum antiviral drug discovery by
relying on the tunability of the α-helical coiled-coil domains
present in all class I fusion proteins and the amphiphilic nature
of the individual helices from this multihelix motif.</p></abstract><custom-meta-group><custom-meta><meta-name>document-id-old-9</meta-name><meta-value>jm8b00890</meta-value></custom-meta><custom-meta><meta-name>document-id-new-14</meta-name><meta-value>jm8b00890</meta-value></custom-meta><custom-meta><meta-name>ccc-price</meta-name><meta-value></meta-value></custom-meta></custom-meta-group></article-meta><notes id="notes-d1e21-autogenerated"><fn-group><fn fn-type="" id="d30e284"><p>This article is made available for a limited time sponsored by ACS under the <ext-link ext-link-type="uri" xlink:href="http://pubs.acs.org/page/policy/freetoread/index.html">ACS Free to Read License</ext-link>, which permits copying and redistribution of the article for non-commercial scholarly purposes.</p></fn></fn-group></notes></front></pmc><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Wang, Chao" sort="Wang, Chao" uniqKey="Wang C" first="Chao" last="Wang">Chao Wang</name></noRegion><name sortKey="Cao, Ruiyuan" sort="Cao, Ruiyuan" uniqKey="Cao R" first="Ruiyuan" last="Cao">Ruiyuan Cao</name><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><name sortKey="Li, Yue" sort="Li, Yue" uniqKey="Li Y" first="Yue" last="Li">Yue Li</name><name sortKey="Liang, Guodong" sort="Liang, Guodong" uniqKey="Liang G" first="Guodong" last="Liang">Guodong Liang</name><name sortKey="Liu, Keliang" sort="Liu, Keliang" uniqKey="Liu K" first="Keliang" last="Liu">Keliang Liu</name><name sortKey="Meng, Guangpeng" sort="Meng, Guangpeng" uniqKey="Meng G" first="Guangpeng" last="Meng">Guangpeng Meng</name><name sortKey="Shi, Weiguo" sort="Shi, Weiguo" uniqKey="Shi W" first="Weiguo" last="Shi">Weiguo Shi</name><name sortKey="Wang, Weicong" sort="Wang, Weicong" uniqKey="Wang W" first="Weicong" last="Wang">Weicong Wang</name><name sortKey="Xia, Shuai" sort="Xia, Shuai" uniqKey="Xia S" first="Shuai" last="Xia">Shuai Xia</name><name sortKey="Zhang, Tianhong" sort="Zhang, Tianhong" uniqKey="Zhang T" first="Tianhong" last="Zhang">Tianhong Zhang</name><name sortKey="Zhao, Lei" sort="Zhao, Lei" uniqKey="Zhao L" first="Lei" last="Zhao">Lei Zhao</name><name sortKey="Zhong, Wu" sort="Zhong, Wu" uniqKey="Zhong W" first="Wu" last="Zhong">Wu Zhong</name></country><country name="États-Unis"><noRegion><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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