Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion
Identifieur interne : 000170 ( Main/Exploration ); précédent : 000169; suivant : 000171Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion
Auteurs : Shuai Xia [République populaire de Chine] ; Meiqin Liu [République populaire de Chine] ; Chao Wang [République populaire de Chine] ; Wei Xu [République populaire de Chine] ; Qiaoshuai Lan [République populaire de Chine] ; Siliang Feng [République populaire de Chine] ; Feifei Qi [République populaire de Chine] ; Linlin Bao [République populaire de Chine] ; Lanying Du [États-Unis] ; Shuwen Liu [République populaire de Chine] ; Chuan Qin [République populaire de Chine] ; Fei Sun [République populaire de Chine] ; Zhengli Shi [République populaire de Chine] ; Yun Zhu [République populaire de Chine] ; Shibo Jiang [République populaire de Chine, États-Unis] ; Lu Lu [République populaire de Chine]Source :
- Cell Research [ 1001-0602 ] ; 2020.
Descripteurs français
- KwdFr :
- Administration par voie nasale, Alignement de séquences, Animaux, Cellules HEK293, Cellules Vero, Fusion cellulaire, Fusion membranaire, Glycoprotéine de spicule des coronavirus (antagonistes et inhibiteurs), Humains, Infections à coronavirus (), Lipopeptides (pharmacologie), Motifs et domaines d'intéraction protéique, Pandémies (), Pneumopathie virale (), Relation structure-activité, Souris, Structure secondaire des protéines, Séquence d'acides aminés, Virus du SRAS.
- MESH :
- antagonistes et inhibiteurs : Glycoprotéine de spicule des coronavirus.
- pharmacologie : Lipopeptides.
- Administration par voie nasale, Alignement de séquences, Animaux, Cellules HEK293, Cellules Vero, Fusion cellulaire, Fusion membranaire, Humains, Infections à coronavirus, Motifs et domaines d'intéraction protéique, Pandémies, Pneumopathie virale, Relation structure-activité, Souris, Structure secondaire des protéines, Séquence d'acides aminés, Virus du SRAS.
English descriptors
- KwdEn :
- Administration, Intranasal, Amino Acid Sequence, Animals, Betacoronavirus (drug effects), Betacoronavirus (physiology), Cell Fusion, Chlorocebus aethiops, Coronavirus Infections (prevention & control), HEK293 Cells, Humans, Lipopeptides (pharmacology), Membrane Fusion, Mice, Pandemics (prevention & control), Pneumonia, Viral (prevention & control), Protein Interaction Domains and Motifs, Protein Structure, Secondary, SARS Virus, Sequence Alignment, Spike Glycoprotein, Coronavirus (antagonists & inhibitors), Structure-Activity Relationship, Vero Cells.
- MESH :
- chemical , antagonists & inhibitors : Spike Glycoprotein, Coronavirus.
- chemical , pharmacology : Lipopeptides.
- drug effects : Betacoronavirus.
- physiology : Betacoronavirus.
- prevention & control : Coronavirus Infections, Pandemics, Pneumonia, Viral.
- Administration, Intranasal, Amino Acid Sequence, Animals, Cell Fusion, Chlorocebus aethiops, HEK293 Cells, Humans, Membrane Fusion, Mice, Protein Interaction Domains and Motifs, Protein Structure, Secondary, SARS Virus, Sequence Alignment, Structure-Activity Relationship, Vero Cells.
Abstract
The recent outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus therapeutics and prophylactics, the molecular mechanism that underlies viral infection must first be defined. Therefore, we herein established a SARS-CoV-2 spike (S) protein-mediated cell–cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted the HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. Here we generated a series of lipopeptides derived from EK1 and found that EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than the original EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, and potently inhibited the replication of 5 live human coronaviruses examined, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs.
Url:
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104723
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118126
DOI: 10.1038/s41422-020-0305-x
PubMed: NONE
PubMed Central: 7104723
Affiliations:
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Le document en format XML
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for Biosafety Mega-Science,</institution><institution>Chinese Academy of Sciences,</institution></institution-wrap>Wuhan, 430071 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Wuhan</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1797 8419</institution-id><institution-id institution-id-type="GRID">grid.410726.6</institution-id><institution>University of Chinese Academy of Sciences,</institution></institution-wrap>Beijing, 100190 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Chao" sort="Wang, Chao" uniqKey="Wang C" first="Chao" last="Wang">Chao Wang</name><affiliation wicri:level="3"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1803 4911</institution-id><institution-id 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University,</institution></institution-wrap>Shanghai, 200032 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Lan, Qiaoshuai" sort="Lan, Qiaoshuai" uniqKey="Lan Q" first="Qiaoshuai" last="Lan">Qiaoshuai Lan</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0125 2443</institution-id><institution-id institution-id-type="GRID">grid.8547.e</institution-id><institution>Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan-Jinbo Joint Research Center,</institution><institution>Fudan University,</institution></institution-wrap>Shanghai, 200032 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Feng, Siliang" sort="Feng, Siliang" uniqKey="Feng S" first="Siliang" last="Feng">Siliang Feng</name><affiliation wicri:level="3"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1803 4911</institution-id><institution-id institution-id-type="GRID">grid.410740.6</institution-id><institution>State Key Laboratory of Toxicology and Medical Countermeasures,</institution><institution>Beijing Institute of Pharmacology and Toxicology,</institution></institution-wrap>27 Tai-Ping Road, Beijing, 100850 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>27 Tai-Ping Road, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Qi, Feifei" sort="Qi, Feifei" uniqKey="Qi F" first="Feifei" last="Qi">Feifei Qi</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center,</institution><institution>Peking Union Medical College,</institution></institution-wrap>Beijing, 100021 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Bao, Linlin" sort="Bao, Linlin" uniqKey="Bao L" first="Linlin" last="Bao">Linlin Bao</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center,</institution><institution>Peking Union Medical College,</institution></institution-wrap>Beijing, 100021 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></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:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0442 2075</institution-id><institution-id institution-id-type="GRID">grid.250415.7</institution-id><institution>Lindsley F. Kimball Research Institute, New York Blood Center,</institution></institution-wrap>New York, NY 10065 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>New York</wicri:cityArea></affiliation></author><author><name sortKey="Liu, Shuwen" sort="Liu, Shuwen" uniqKey="Liu S" first="Shuwen" last="Liu">Shuwen Liu</name><affiliation wicri:level="1"><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 8877 7471</institution-id><institution-id institution-id-type="GRID">grid.284723.8</institution-id><institution>Guangdong Provincial Key Laboratory of New Drug Screening,</institution><institution>Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University,</institution></institution-wrap>Guangzhou, 510515 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangzhou</wicri:regionArea></affiliation></author><author><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center,</institution><institution>Peking Union Medical College,</institution></institution-wrap>Beijing, 100021 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Sun, Fei" sort="Sun, Fei" uniqKey="Sun F" first="Fei" last="Sun">Fei Sun</name><affiliation wicri:level="1"><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1792 5640</institution-id><institution-id institution-id-type="GRID">grid.418856.6</institution-id><institution>National Laboratory of Biomacromolecules,</institution><institution>Institute of Biophysics, Chinese Academy of Sciences,</institution></institution-wrap>Beijing, 100101 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Shi, Zhengli" sort="Shi, Zhengli" uniqKey="Shi Z" first="Zhengli" last="Shi">Zhengli Shi</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000000119573309</institution-id><institution-id institution-id-type="GRID">grid.9227.e</institution-id><institution>CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science,</institution><institution>Chinese Academy of Sciences,</institution></institution-wrap>Wuhan, 430071 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Wuhan</wicri:regionArea></affiliation></author><author><name sortKey="Zhu, Yun" sort="Zhu, Yun" uniqKey="Zhu Y" first="Yun" last="Zhu">Yun Zhu</name><affiliation wicri:level="1"><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1792 5640</institution-id><institution-id institution-id-type="GRID">grid.418856.6</institution-id><institution>National Laboratory of Biomacromolecules,</institution><institution>Institute of Biophysics, Chinese Academy of Sciences,</institution></institution-wrap>Beijing, 100101 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</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="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0125 2443</institution-id><institution-id institution-id-type="GRID">grid.8547.e</institution-id><institution>Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan-Jinbo Joint Research Center,</institution><institution>Fudan University,</institution></institution-wrap>Shanghai, 200032 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shanghai</wicri:regionArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0442 2075</institution-id><institution-id institution-id-type="GRID">grid.250415.7</institution-id><institution>Lindsley F. Kimball Research Institute, New York Blood Center,</institution></institution-wrap>New York, NY 10065 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>New York</wicri:cityArea></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:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0125 2443</institution-id><institution-id institution-id-type="GRID">grid.8547.e</institution-id><institution>Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan-Jinbo Joint Research Center,</institution><institution>Fudan University,</institution></institution-wrap>Shanghai, 200032 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shanghai</wicri:regionArea></affiliation></author></analytic><series><title level="j">Cell Research</title><idno type="ISSN">1001-0602</idno><idno type="eISSN">1748-7838</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Administration, Intranasal</term><term>Amino Acid Sequence</term><term>Animals</term><term>Betacoronavirus (drug effects)</term><term>Betacoronavirus (physiology)</term><term>Cell Fusion</term><term>Chlorocebus aethiops</term><term>Coronavirus Infections (prevention & control)</term><term>HEK293 Cells</term><term>Humans</term><term>Lipopeptides (pharmacology)</term><term>Membrane Fusion</term><term>Mice</term><term>Pandemics (prevention & control)</term><term>Pneumonia, Viral (prevention & control)</term><term>Protein Interaction Domains and Motifs</term><term>Protein Structure, Secondary</term><term>SARS Virus</term><term>Sequence Alignment</term><term>Spike Glycoprotein, Coronavirus (antagonists & inhibitors)</term><term>Structure-Activity Relationship</term><term>Vero Cells</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Administration par voie nasale</term><term>Alignement de séquences</term><term>Animaux</term><term>Cellules HEK293</term><term>Cellules Vero</term><term>Fusion cellulaire</term><term>Fusion membranaire</term><term>Glycoprotéine de spicule des coronavirus (antagonistes et inhibiteurs)</term><term>Humains</term><term>Infections à coronavirus ()</term><term>Lipopeptides (pharmacologie)</term><term>Motifs et domaines d'intéraction protéique</term><term>Pandémies ()</term><term>Pneumopathie virale ()</term><term>Relation structure-activité</term><term>Souris</term><term>Structure secondaire des protéines</term><term>Séquence d'acides aminés</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Lipopeptides</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Glycoprotéine de spicule des coronavirus</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Betacoronavirus</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Lipopeptides</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Betacoronavirus</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Coronavirus Infections</term><term>Pandemics</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Administration, Intranasal</term><term>Amino Acid Sequence</term><term>Animals</term><term>Cell Fusion</term><term>Chlorocebus aethiops</term><term>HEK293 Cells</term><term>Humans</term><term>Membrane Fusion</term><term>Mice</term><term>Protein Interaction Domains and Motifs</term><term>Protein Structure, Secondary</term><term>SARS Virus</term><term>Sequence Alignment</term><term>Structure-Activity Relationship</term><term>Vero Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Administration par voie nasale</term><term>Alignement de séquences</term><term>Animaux</term><term>Cellules HEK293</term><term>Cellules Vero</term><term>Fusion cellulaire</term><term>Fusion membranaire</term><term>Humains</term><term>Infections à coronavirus</term><term>Motifs et domaines d'intéraction protéique</term><term>Pandémies</term><term>Pneumopathie virale</term><term>Relation structure-activité</term><term>Souris</term><term>Structure secondaire des protéines</term><term>Séquence d'acides aminés</term><term>Virus du SRAS</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">The recent outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus therapeutics and prophylactics, the molecular mechanism that underlies viral infection must first be defined. Therefore, we herein established a SARS-CoV-2 spike (S) protein-mediated cell–cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted the HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. Here we generated a series of lipopeptides derived from EK1 and found that EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than the original EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, and potently inhibited the replication of 5 live human coronaviruses examined, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, N" uniqKey="Zhu N">N Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, F" uniqKey="Wu F">F Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, P" uniqKey="Zhou P">P Zhou</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Jiang, S" uniqKey="Jiang S">S Jiang</name></author><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author><author><name sortKey="Shi, Z" uniqKey="Shi Z">Z Shi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, C" uniqKey="Huang C">C Huang</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Wrapp, D" uniqKey="Wrapp D">D Wrapp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bosch, Bj" uniqKey="Bosch B">BJ Bosch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xia, S" uniqKey="Xia S">S Xia</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Lu, L" uniqKey="Lu L">L Lu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, S" uniqKey="Liu S">S Liu</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Mathieu, C" uniqKey="Mathieu C">C Mathieu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Garten, Rj" uniqKey="Garten R">RJ Garten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anderson, Lj" uniqKey="Anderson L">LJ Anderson</name></author><author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Howard, Cr" uniqKey="Howard C">CR Howard</name></author><author><name sortKey="Fletcher, Nf" uniqKey="Fletcher N">NF Fletcher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shirato, K" uniqKey="Shirato K">K Shirato</name></author><author><name sortKey="Kanou, K" uniqKey="Kanou K">K Kanou</name></author><author><name sortKey="Kawase, M" uniqKey="Kawase M">M Kawase</name></author><author><name sortKey="Matsuyama, S" uniqKey="Matsuyama S">S Matsuyama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shirato, K" uniqKey="Shirato K">K Shirato</name></author><author><name sortKey="Kawase, M" uniqKey="Kawase M">M Kawase</name></author><author><name sortKey="Matsuyama, S" uniqKey="Matsuyama S">S Matsuyama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Belouzard, S" uniqKey="Belouzard S">S Belouzard</name></author><author><name sortKey="Chu, Vc" uniqKey="Chu V">VC Chu</name></author><author><name sortKey="Whittaker, Gr" uniqKey="Whittaker G">GR Whittaker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Follis, Ke" uniqKey="Follis K">KE Follis</name></author><author><name sortKey="York, J" uniqKey="York J">J York</name></author><author><name sortKey="Nunberg, Jh" uniqKey="Nunberg J">JH Nunberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hoffmann, M" uniqKey="Hoffmann M">M Hoffmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hollmann, A" uniqKey="Hollmann A">A Hollmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Channappanavar, R" uniqKey="Channappanavar R">R Channappanavar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jacomy, H" uniqKey="Jacomy H">H Jacomy</name></author><author><name sortKey="Talbot, Pj" uniqKey="Talbot P">PJ Talbot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, M" uniqKey="Wang M">M Wang</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Xia, S" uniqKey="Xia S">S Xia</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Battye, Tg" uniqKey="Battye T">TG Battye</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liebschner, D" uniqKey="Liebschner D">D Liebschner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vagin, Aa" uniqKey="Vagin A">AA Vagin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Waterhouse, A" uniqKey="Waterhouse A">A Waterhouse</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Morris, Gm" uniqKey="Morris G">GM Morris</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>État de New York</li></region><settlement><li>Pékin</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Xia, Shuai" sort="Xia, Shuai" uniqKey="Xia S" first="Shuai" last="Xia">Shuai Xia</name></noRegion><name sortKey="Bao, Linlin" sort="Bao, Linlin" uniqKey="Bao L" first="Linlin" last="Bao">Linlin Bao</name><name sortKey="Feng, Siliang" sort="Feng, Siliang" uniqKey="Feng S" first="Siliang" last="Feng">Siliang Feng</name><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><name sortKey="Lan, Qiaoshuai" sort="Lan, Qiaoshuai" uniqKey="Lan Q" first="Qiaoshuai" last="Lan">Qiaoshuai Lan</name><name sortKey="Liu, Meiqin" sort="Liu, Meiqin" uniqKey="Liu M" first="Meiqin" last="Liu">Meiqin Liu</name><name sortKey="Liu, Meiqin" sort="Liu, Meiqin" uniqKey="Liu M" first="Meiqin" last="Liu">Meiqin Liu</name><name sortKey="Liu, Shuwen" sort="Liu, Shuwen" uniqKey="Liu S" first="Shuwen" last="Liu">Shuwen Liu</name><name sortKey="Lu, Lu" sort="Lu, Lu" uniqKey="Lu L" first="Lu" last="Lu">Lu Lu</name><name sortKey="Qi, Feifei" sort="Qi, Feifei" uniqKey="Qi F" first="Feifei" last="Qi">Feifei Qi</name><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name><name sortKey="Shi, Zhengli" sort="Shi, Zhengli" uniqKey="Shi Z" first="Zhengli" last="Shi">Zhengli Shi</name><name sortKey="Sun, Fei" sort="Sun, Fei" uniqKey="Sun F" first="Fei" last="Sun">Fei Sun</name><name sortKey="Wang, Chao" sort="Wang, Chao" uniqKey="Wang C" first="Chao" last="Wang">Chao Wang</name><name sortKey="Xu, Wei" sort="Xu, Wei" uniqKey="Xu W" first="Wei" last="Xu">Wei Xu</name><name sortKey="Zhu, Yun" sort="Zhu, Yun" uniqKey="Zhu Y" first="Yun" last="Zhu">Yun Zhu</name></country><country name="États-Unis"><region name="État de New York"><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name></region><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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