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A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike

Identifieur interne : 002191 ( Ncbi/Merge ); précédent : 002190; suivant : 002192

A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike

Auteurs : Shuai Xia [République populaire de Chine] ; Lei Yan [République populaire de Chine] ; Wei Xu [République populaire de Chine] ; Anurodh Shankar Agrawal [États-Unis] ; Abdullah Algaissi [États-Unis, Arabie saoudite] ; Chien-Te K. Tseng [États-Unis] ; Qian Wang [République populaire de Chine] ; Lanying Du [États-Unis] ; Wenjie Tan [République populaire de Chine] ; Ian A. Wilson [République populaire de Chine, États-Unis] ; Shibo Jiang [République populaire de Chine, États-Unis] ; Bei Yang [République populaire de Chine] ; Lu Lu [République populaire de Chine]

Source :

RBID : PMC:6457931

Abstract

EK1 is a broad-spectrum human coronavirus fusion inhibitor for combating infection of current and emerging coronaviruses.


Url:
DOI: 10.1126/sciadv.aav4580
PubMed: 30989115
PubMed Central: 6457931

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PMC:6457931

Le document en format XML

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<name sortKey="Yang, Bei" sort="Yang, Bei" uniqKey="Yang B" first="Bei" last="Yang">Bei Yang</name>
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<name sortKey="Lu, Lu" sort="Lu, Lu" uniqKey="Lu L" first="Lu" last="Lu">Lu Lu</name>
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<title level="j">Science Advances</title>
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<p>EK1 is a broad-spectrum human coronavirus fusion inhibitor for combating infection of current and emerging coronaviruses.</p>
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<name sortKey="Woo, P C Y" uniqKey="Woo P">P. C. Y. Woo</name>
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<title xml:lang="en" level="a" type="main">A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike</title>
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<author>
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</affiliation>
<affiliation wicri:level="2">
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<region type="state">Californie</region>
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<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="aff1">Shanghai Public Health Clinical Center and School of Basic Medical Sciences, and Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai 200032, China.</nlm:aff>
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<nlm:aff id="aff2">Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
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<nlm:aff id="aff1">Shanghai Public Health Clinical Center and School of Basic Medical Sciences, and Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai 200032, China.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
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<front>
<div type="abstract" xml:lang="en">
<p>EK1 is a broad-spectrum human coronavirus fusion inhibitor for combating infection of current and emerging coronaviruses.</p>
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<name sortKey="Algaissi, Abdullah" sort="Algaissi, Abdullah" uniqKey="Algaissi A" first="Abdullah" last="Algaissi">Abdullah Algaissi</name>
<affiliation wicri:level="2">
<nlm:affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555</wicri:regionArea>
<placeName>
<region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K" last="Tseng">Chien-Te K. Tseng</name>
<affiliation wicri:level="2">
<nlm:affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555</wicri:regionArea>
<placeName>
<region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Wang, Qian" sort="Wang, Qian" uniqKey="Wang Q" first="Qian" last="Wang">Qian Wang</name>
<affiliation wicri:level="1">
<nlm:affiliation>Shanghai Public Health Clinical Center and School of Basic Medical Sciences, and Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shanghai Public Health Clinical Center and School of Basic Medical Sciences, and Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name>
<affiliation wicri:level="2">
<nlm:affiliation>Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065</wicri:regionArea>
<placeName>
<region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name>
<affiliation wicri:level="3">
<nlm:affiliation>MOH Key Laboratory of Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>MOH Key Laboratory of Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing</wicri:regionArea>
<placeName>
<settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A" last="Wilson">Ian A. Wilson</name>
<affiliation wicri:level="1">
<nlm:affiliation>Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210</wicri:regionArea>
<wicri:noRegion>Shanghai 201210</wicri:noRegion>
</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:affiliation>Shanghai Public Health Clinical Center and School of Basic Medical Sciences, and Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shanghai Public Health Clinical Center and School of Basic Medical Sciences, and Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Yang, Bei" sort="Yang, Bei" uniqKey="Yang B" first="Bei" last="Yang">Bei Yang</name>
<affiliation wicri:level="1">
<nlm:affiliation>Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210</wicri:regionArea>
<wicri:noRegion>Shanghai 201210</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Lu, Lu" sort="Lu, Lu" uniqKey="Lu L" first="Lu" last="Lu">Lu Lu</name>
<affiliation wicri:level="1">
<nlm:affiliation>Shanghai Public Health Clinical Center and School of Basic Medical Sciences, and Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shanghai Public Health Clinical Center and School of Basic Medical Sciences, and Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Science advances</title>
<idno type="eISSN">2375-2548</idno>
<imprint>
<date when="2019" type="published">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Continuously emerging highly pathogenic human coronaviruses (HCoVs) remain a major threat to human health, as illustrated in past SARS-CoV and MERS-CoV outbreaks. The development of a drug with broad-spectrum HCoV inhibitory activity would address this urgent unmet medical need. Although previous studies have suggested that the HR1 of HCoV spike (S) protein is an important target site for inhibition against specific HCoVs, whether this conserved region could serve as a target for the development of broad-spectrum pan-CoV inhibitor remains controversial. Here, we found that peptide OC43-HR2P, derived from the HR2 domain of HCoV-OC43, exhibited broad fusion inhibitory activity against multiple HCoVs. EK1, the optimized form of OC43-HR2P, showed substantially improved pan-CoV fusion inhibitory activity and pharmaceutical properties. Crystal structures indicated that EK1 can form a stable six-helix bundle structure with both short α-HCoV and long β-HCoV HR1s, further supporting the role of HR1 region as a viable pan-CoV target site.</div>
</front>
</TEI>
</pubmed>
</double>
</record>

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