A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV
Identifieur interne : 000E99 ( Pmc/Curation ); précédent : 000E98; suivant : 000F00A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV
Auteurs : Guangyu Zhao [République populaire de Chine] ; Lei He [République populaire de Chine] ; Shihui Sun [République populaire de Chine] ; Hongjie Qiu [République populaire de Chine] ; Wanbo Tai [République populaire de Chine, États-Unis] ; Jiawei Chen [États-Unis] ; Jiangfan Li [République populaire de Chine] ; Yuehong Chen [République populaire de Chine] ; Yan Guo [République populaire de Chine] ; Yufei Wang [États-Unis] ; Jian Shang [États-Unis] ; Kaiyuan Ji [République populaire de Chine] ; Ruiwen Fan [République populaire de Chine] ; Enqi Du [République populaire de Chine] ; Shibo Jiang [États-Unis] ; Fang Li [États-Unis] ; Lanying Du [États-Unis] ; Yusen Zhou [République populaire de Chine]Source :
- Journal of Virology [ 0022-538X ] ; 2018.
Abstract
Therapeutic development is critical for preventing and treating continual MERS-CoV infections in humans and camels. Because of their small size, nanobodies (Nbs) have advantages as antiviral therapeutics (e.g., high expression yield and robustness for storage and transportation) and also potential limitations (e.g., low antigen-binding affinity and fast renal clearance). Here, we have developed novel Nbs that specifically target the receptor-binding domain (RBD) of MERS-CoV spike protein. They bind to a conserved site on MERS-CoV RBD with high affinity, blocking RBD's binding to MERS-CoV receptor. Through engineering a C-terminal human Fc tag, the
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DOI: 10.1128/JVI.00837-18
PubMed: 29950421
PubMed Central: 6146697
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV</title><author><name sortKey="Zhao, Guangyu" sort="Zhao, Guangyu" uniqKey="Zhao G" first="Guangyu" last="Zhao">Guangyu Zhao</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="He, Lei" sort="He, Lei" uniqKey="He L" first="Lei" last="He">Lei He</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Sun, Shihui" sort="Sun, Shihui" uniqKey="Sun S" first="Shihui" last="Sun">Shihui Sun</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Qiu, Hongjie" sort="Qiu, Hongjie" uniqKey="Qiu H" first="Hongjie" last="Qiu">Hongjie Qiu</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Tai, Wanbo" sort="Tai, Wanbo" uniqKey="Tai W" first="Wanbo" last="Tai">Wanbo Tai</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Jiawei" sort="Chen, Jiawei" uniqKey="Chen J" first="Jiawei" last="Chen">Jiawei Chen</name><affiliation wicri:level="1"><nlm:aff id="aff2">Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea></affiliation></author><author><name sortKey="Li, Jiangfan" sort="Li, Jiangfan" uniqKey="Li J" first="Jiangfan" last="Li">Jiangfan Li</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Yuehong" sort="Chen, Yuehong" uniqKey="Chen Y" first="Yuehong" last="Chen">Yuehong Chen</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Guo, Yan" sort="Guo, Yan" uniqKey="Guo Y" first="Yan" last="Guo">Yan Guo</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Yufei" sort="Wang, Yufei" uniqKey="Wang Y" first="Yufei" last="Wang">Yufei Wang</name><affiliation wicri:level="1"><nlm:aff id="aff2">Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea></affiliation></author><author><name sortKey="Shang, Jian" sort="Shang, Jian" uniqKey="Shang J" first="Jian" last="Shang">Jian Shang</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota</wicri:regionArea></affiliation></author><author><name sortKey="Ji, Kaiyuan" sort="Ji, Kaiyuan" uniqKey="Ji K" first="Kaiyuan" last="Ji">Kaiyuan Ji</name><affiliation wicri:level="1"><nlm:aff id="aff4">ShanXi Agricultural University, Shanxi, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>ShanXi Agricultural University, Shanxi</wicri:regionArea></affiliation></author><author><name sortKey="Fan, Ruiwen" sort="Fan, Ruiwen" uniqKey="Fan R" first="Ruiwen" last="Fan">Ruiwen Fan</name><affiliation wicri:level="1"><nlm:aff id="aff4">ShanXi Agricultural University, Shanxi, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>ShanXi Agricultural University, Shanxi</wicri:regionArea></affiliation></author><author><name sortKey="Du, Enqi" sort="Du, Enqi" uniqKey="Du E" first="Enqi" last="Du">Enqi Du</name><affiliation wicri:level="1"><nlm:aff id="aff5">Northwest A&F University, Shaanxi, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Northwest A&F University, Shaanxi</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">Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea></affiliation></author><author><name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota</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="1"><nlm:aff id="aff2">Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea></affiliation></author><author><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6">Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">29950421</idno><idno type="pmc">6146697</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146697</idno><idno type="RBID">PMC:6146697</idno><idno type="doi">10.1128/JVI.00837-18</idno><date when="2018">2018</date><idno type="wicri:Area/Pmc/Corpus">000E99</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000E99</idno><idno type="wicri:Area/Pmc/Curation">000E99</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000E99</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV</title><author><name sortKey="Zhao, Guangyu" sort="Zhao, Guangyu" uniqKey="Zhao G" first="Guangyu" last="Zhao">Guangyu Zhao</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="He, Lei" sort="He, Lei" uniqKey="He L" first="Lei" last="He">Lei He</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Sun, Shihui" sort="Sun, Shihui" uniqKey="Sun S" first="Shihui" last="Sun">Shihui Sun</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Qiu, Hongjie" sort="Qiu, Hongjie" uniqKey="Qiu H" first="Hongjie" last="Qiu">Hongjie Qiu</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Tai, Wanbo" sort="Tai, Wanbo" uniqKey="Tai W" first="Wanbo" last="Tai">Wanbo Tai</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Jiawei" sort="Chen, Jiawei" uniqKey="Chen J" first="Jiawei" last="Chen">Jiawei Chen</name><affiliation wicri:level="1"><nlm:aff id="aff2">Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea></affiliation></author><author><name sortKey="Li, Jiangfan" sort="Li, Jiangfan" uniqKey="Li J" first="Jiangfan" last="Li">Jiangfan Li</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Yuehong" sort="Chen, Yuehong" uniqKey="Chen Y" first="Yuehong" last="Chen">Yuehong Chen</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Guo, Yan" sort="Guo, Yan" uniqKey="Guo Y" first="Yan" last="Guo">Yan Guo</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Yufei" sort="Wang, Yufei" uniqKey="Wang Y" first="Yufei" last="Wang">Yufei Wang</name><affiliation wicri:level="1"><nlm:aff id="aff2">Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea></affiliation></author><author><name sortKey="Shang, Jian" sort="Shang, Jian" uniqKey="Shang J" first="Jian" last="Shang">Jian Shang</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota</wicri:regionArea></affiliation></author><author><name sortKey="Ji, Kaiyuan" sort="Ji, Kaiyuan" uniqKey="Ji K" first="Kaiyuan" last="Ji">Kaiyuan Ji</name><affiliation wicri:level="1"><nlm:aff id="aff4">ShanXi Agricultural University, Shanxi, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>ShanXi Agricultural University, Shanxi</wicri:regionArea></affiliation></author><author><name sortKey="Fan, Ruiwen" sort="Fan, Ruiwen" uniqKey="Fan R" first="Ruiwen" last="Fan">Ruiwen Fan</name><affiliation wicri:level="1"><nlm:aff id="aff4">ShanXi Agricultural University, Shanxi, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>ShanXi Agricultural University, Shanxi</wicri:regionArea></affiliation></author><author><name sortKey="Du, Enqi" sort="Du, Enqi" uniqKey="Du E" first="Enqi" last="Du">Enqi Du</name><affiliation wicri:level="1"><nlm:aff id="aff5">Northwest A&F University, Shaanxi, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Northwest A&F University, Shaanxi</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">Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea></affiliation></author><author><name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota</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="1"><nlm:aff id="aff2">Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea></affiliation></author><author><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6">Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou</wicri:regionArea></affiliation></author></analytic><series><title level="j">Journal of Virology</title><idno type="ISSN">0022-538X</idno><idno type="eISSN">1098-5514</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>Therapeutic development is critical for preventing and treating continual MERS-CoV infections in humans and camels. Because of their small size, nanobodies (Nbs) have advantages as antiviral therapeutics (e.g., high expression yield and robustness for storage and transportation) and also potential limitations (e.g., low antigen-binding affinity and fast renal clearance). Here, we have developed novel Nbs that specifically target the receptor-binding domain (RBD) of MERS-CoV spike protein. They bind to a conserved site on MERS-CoV RBD with high affinity, blocking RBD's binding to MERS-CoV receptor. Through engineering a C-terminal human Fc tag, the <italic>in vivo</italic> half-life of the Nbs is significantly extended. Moreover, the Nbs can potently cross-neutralize the infections of diverse MERS-CoV strains isolated from humans and camels. The Fc-tagged Nb also completely protects humanized mice from lethal MERS-CoV challenge. Taken together, our study has discovered novel Nbs that hold promise as potent, cost-effective, and broad-spectrum anti-MERS-CoV therapeutic agents.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Konning, D" uniqKey="Konning D">D Konning</name></author><author><name sortKey="Zielonka, S" uniqKey="Zielonka S">S Zielonka</name></author><author><name sortKey="Grzeschik, J" uniqKey="Grzeschik J">J Grzeschik</name></author><author><name sortKey="Empting, M" uniqKey="Empting M">M Empting</name></author><author><name sortKey="Valldorf, B" uniqKey="Valldorf B">B Valldorf</name></author><author><name sortKey="Krah, S" uniqKey="Krah S">S Krah</name></author><author><name sortKey="Schroter, C" uniqKey="Schroter C">C Schroter</name></author><author><name sortKey="Sellmann, C" uniqKey="Sellmann C">C Sellmann</name></author><author><name sortKey="Hock, B" uniqKey="Hock B">B Hock</name></author><author><name sortKey="Kolmar, H" uniqKey="Kolmar 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Virol</journal-id><journal-id journal-id-type="iso-abbrev">J. Virol</journal-id><journal-id journal-id-type="hwp">jvi</journal-id><journal-id journal-id-type="pmc">jvi</journal-id><journal-id journal-id-type="publisher-id">JVI</journal-id><journal-title-group><journal-title>Journal of Virology</journal-title></journal-title-group><issn pub-type="ppub">0022-538X</issn><issn pub-type="epub">1098-5514</issn><publisher><publisher-name>American Society for Microbiology</publisher-name><publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">29950421</article-id><article-id pub-id-type="pmc">6146697</article-id><article-id pub-id-type="publisher-id">00837-18</article-id><article-id pub-id-type="doi">10.1128/JVI.00837-18</article-id><article-categories><subj-group subj-group-type="heading"><subject>Vaccines and Antiviral Agents</subject></subj-group></article-categories><title-group><article-title>A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV</article-title><alt-title alt-title-type="running-head">Anti-MERS-CoV Nanobody with Protective Efficacy</alt-title><alt-title alt-title-type="short-authors">Zhao et al.</alt-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Zhao</surname><given-names>Guangyu</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>He</surname><given-names>Lei</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Sun</surname><given-names>Shihui</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Qiu</surname><given-names>Hongjie</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Tai</surname><given-names>Wanbo</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Chen</surname><given-names>Jiawei</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Li</surname><given-names>Jiangfan</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Chen</surname><given-names>Yuehong</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Guo</surname><given-names>Yan</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Wang</surname><given-names>Yufei</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Shang</surname><given-names>Jian</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Ji</surname><given-names>Kaiyuan</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Fan</surname><given-names>Ruiwen</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Du</surname><given-names>Enqi</given-names></name><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Jiang</surname><given-names>Shibo</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Li</surname><given-names>Fang</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author" corresp="yes" equal-contrib="yes"><name><surname>Du</surname><given-names>Lanying</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author" corresp="yes" equal-contrib="yes"><name><surname>Zhou</surname><given-names>Yusen</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff6"><sup>f</sup></xref></contrib><aff id="aff1"><label>a</label>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</aff><aff id="aff2"><label>b</label>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA</aff><aff id="aff3"><label>c</label>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</aff><aff id="aff4"><label>d</label>ShanXi Agricultural University, Shanxi, China</aff><aff id="aff5"><label>e</label>Northwest A&F University, Shaanxi, China</aff><aff id="aff6"><label>f</label>Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China</aff></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Gallagher</surname><given-names>Tom</given-names></name><role>Editor</role><aff>Loyola University Medical Center</aff></contrib></contrib-group><author-notes><corresp id="cor1">Address correspondence to Lanying Du, <email>ldu@nybc.org</email>, or Yusen Zhou, <email>yszhou@bmi.ac.cn</email>.</corresp><fn fn-type="equal"><p>F.L., L.D., and Y.Z. are co-senior authors of the paper and contributed equally to this article. G.Z., L.H., and S.S. contributed equally to this article.</p></fn><fn fn-type="other"><p><bold>Citation</bold> Zhao G, He L, Sun S, Qiu H, Tai W, Chen J, Li J, Chen Y, Guo Y, Wang Y, Shang J, Ji K, Fan R, Du E, Jiang S, Li F, Du L, Zhou Y. 2018. A novel nanobody targeting Middle East respiratory syndrome coronavirus (MERS-CoV) receptor-binding domain has potent cross-neutralizing activity and protective efficacy against MERS-CoV. J Virol 92:e00837-18. <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/JVI.00837-18">https://doi.org/10.1128/JVI.00837-18</ext-link>.</p></fn></author-notes><pub-date pub-type="epreprint"><day>27</day><month>6</month><year>2018</year></pub-date><pub-date pub-type="epub"><day>29</day><month>8</month><year>2018</year></pub-date><pub-date pub-type="collection"><day>15</day><month>9</month><year>2018</year></pub-date><pub-date pub-type="pmc-release"><day>29</day><month>8</month><year>2018</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>92</volume><issue>18</issue><elocation-id>e00837-18</elocation-id><history><date date-type="received"><day>11</day><month>5</month><year>2018</year></date><date date-type="accepted"><day>25</day><month>6</month><year>2018</year></date></history><permissions><copyright-statement>Copyright © 2018 Zhao et al.</copyright-statement><copyright-year>2018</copyright-year><copyright-holder>Zhao et al.</copyright-holder><license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license</ext-link>.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="zjv018183844001.pdf"></self-uri><abstract abstract-type="precis"><p>Therapeutic development is critical for preventing and treating continual MERS-CoV infections in humans and camels. Because of their small size, nanobodies (Nbs) have advantages as antiviral therapeutics (e.g., high expression yield and robustness for storage and transportation) and also potential limitations (e.g., low antigen-binding affinity and fast renal clearance). Here, we have developed novel Nbs that specifically target the receptor-binding domain (RBD) of MERS-CoV spike protein. They bind to a conserved site on MERS-CoV RBD with high affinity, blocking RBD's binding to MERS-CoV receptor. Through engineering a C-terminal human Fc tag, the <italic>in vivo</italic> half-life of the Nbs is significantly extended. Moreover, the Nbs can potently cross-neutralize the infections of diverse MERS-CoV strains isolated from humans and camels. The Fc-tagged Nb also completely protects humanized mice from lethal MERS-CoV challenge. Taken together, our study has discovered novel Nbs that hold promise as potent, cost-effective, and broad-spectrum anti-MERS-CoV therapeutic agents.</p></abstract><abstract><title>ABSTRACT</title><p>The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) continues to infect humans and camels, calling for efficient, cost-effective, and broad-spectrum strategies to control its spread. Nanobodies (Nbs) are single-domain antibodies derived from camelids and sharks and are potentially cost-effective antivirals with small size and great expression yield. In this study, we developed a novel neutralizing Nb (NbMS10) and its human-Fc-fused version (NbMS10-Fc), both of which target the MERS-CoV spike protein receptor-binding domain (RBD). We further tested their receptor-binding affinity, recognizing epitopes, cross-neutralizing activity, half-life, and efficacy against MERS-CoV infection. Both Nbs can be expressed in yeasts with high yield, bind to MERS-CoV RBD with high affinity, and block the binding of MERS-CoV RBD to the MERS-CoV receptor. The binding site of the Nbs on the RBD was mapped to be around residue Asp539, which is part of a conserved conformational epitope at the receptor-binding interface. NbMS10 and NbMS10-Fc maintained strong cross-neutralizing activity against divergent MERS-CoV strains isolated from humans and camels. Particularly, NbMS10-Fc had significantly extended half-life <italic>in vivo</italic>; a single-dose treatment of NbMS10-Fc exhibited high prophylactic and therapeutic efficacy by completely protecting humanized mice from lethal MERS-CoV challenge. Overall, this study proves the feasibility of producing cost-effective, potent, and broad-spectrum Nbs against MERS-CoV and has produced Nbs with great potentials as anti-MERS-CoV therapeutics.</p><p><bold>IMPORTANCE</bold> Therapeutic development is critical for preventing and treating continual MERS-CoV infections in humans and camels. Because of their small size, nanobodies (Nbs) have advantages as antiviral therapeutics (e.g., high expression yield and robustness for storage and transportation) and also potential limitations (e.g., low antigen-binding affinity and fast renal clearance). Here, we have developed novel Nbs that specifically target the receptor-binding domain (RBD) of MERS-CoV spike protein. They bind to a conserved site on MERS-CoV RBD with high affinity, blocking RBD's binding to MERS-CoV receptor. Through engineering a C-terminal human Fc tag, the <italic>in vivo</italic> half-life of the Nbs is significantly extended. Moreover, the Nbs can potently cross-neutralize the infections of diverse MERS-CoV strains isolated from humans and camels. The Fc-tagged Nb also completely protects humanized mice from lethal MERS-CoV challenge. Taken together, our study has discovered novel Nbs that hold promise as potent, cost-effective, and broad-spectrum anti-MERS-CoV therapeutic agents.</p></abstract><kwd-group><title>KEYWORDS</title><kwd>MERS-CoV</kwd><kwd>spike protein</kwd><kwd>receptor-binding domain</kwd><kwd>nanobody</kwd><kwd>cross-neutralization</kwd><kwd>protective efficacy</kwd></kwd-group><funding-group><award-group id="award1"><funding-source id="gs1"><institution-wrap><institution>Technology Innovation Fund in China</institution></institution-wrap></funding-source><award-id rid="gs1">3407049</award-id><principal-award-recipient><name><surname>Zhao</surname><given-names>Guangyu</given-names></name></principal-award-recipient></award-group><award-group id="award2"><funding-source id="gs2"><institution-wrap><institution>State Key Laboratory of Pathogen and Biosecurity</institution></institution-wrap></funding-source><award-id rid="gs2">SKLPBS1704</award-id><principal-award-recipient><name><surname>Zhao</surname><given-names>Guangyu</given-names></name></principal-award-recipient></award-group><award-group id="award3"><funding-source id="gs3"><institution-wrap><institution>Technology Innovation Fund in China</institution></institution-wrap></funding-source><award-id rid="gs3">3407049</award-id><principal-award-recipient><name><surname>Zhou</surname><given-names>Yusen</given-names></name></principal-award-recipient></award-group><award-group id="award4"><funding-source id="gs4"><institution-wrap><institution>State Key Laboratory of Pathogen and Biosecurity</institution></institution-wrap></funding-source><award-id rid="gs4">SKLPBS1704</award-id><principal-award-recipient><name><surname>Zhou</surname><given-names>Yusen</given-names></name></principal-award-recipient></award-group><award-group id="award5"><funding-source id="gs5"><institution-wrap><institution>National Key Plan for Scientific Research and Development of China</institution></institution-wrap></funding-source><award-id rid="gs5">2016YFD0500306</award-id><award-id rid="gs5">NSFC81571983</award-id><principal-award-recipient><name><surname>Zhao</surname><given-names>Guangyu</given-names></name></principal-award-recipient></award-group><award-group id="award6"><funding-source id="gs6"><institution-wrap><institution>National Key Plan for Scientific Research and Development of China</institution></institution-wrap></funding-source><award-id rid="gs6">2016YFD0500306</award-id><award-id rid="gs6">NSFC81571983</award-id><principal-award-recipient><name><surname>Zhou</surname><given-names>Yusen</given-names></name></principal-award-recipient></award-group><award-group id="award7"><funding-source id="gs7"><institution-wrap><institution>HHS | National Institutes of Health (NIH)</institution><institution-id>https://doi.org/10.13039/100000002</institution-id></institution-wrap></funding-source><award-id rid="gs7">R01AI137472</award-id><award-id rid="gs7">R21AI109094</award-id><award-id rid="gs7">R21AI128311</award-id><award-id rid="gs7">R01AI139092</award-id><principal-award-recipient><name><surname>Du</surname><given-names>Lanying</given-names></name></principal-award-recipient></award-group><award-group id="award8"><funding-source id="gs8"><institution-wrap><institution>HHS | National Institutes of Health (NIH)</institution><institution-id>https://doi.org/10.13039/100000002</institution-id></institution-wrap></funding-source><award-id rid="gs8">R01AI137472</award-id><award-id rid="gs8">R21AI109094</award-id><award-id rid="gs8">R21AI128311</award-id><award-id rid="gs8">R01AI139092</award-id><principal-award-recipient><name><surname>Jiang</surname><given-names>Shibo</given-names></name></principal-award-recipient></award-group><award-group id="award9"><funding-source id="gs9"><institution-wrap><institution>HHS | National Institutes of Health (NIH)</institution><institution-id>https://doi.org/10.13039/100000002</institution-id></institution-wrap></funding-source><award-id rid="gs9">R01AI089728</award-id><award-id rid="gs9">R01AI110700</award-id><award-id rid="gs9">R01AI139092</award-id><principal-award-recipient><name><surname>Li</surname><given-names>Fang</given-names></name></principal-award-recipient></award-group></funding-group><counts><fig-count count="8"></fig-count><table-count count="1"></table-count><equation-count count="0"></equation-count><ref-count count="55"></ref-count><page-count count="15"></page-count><word-count count="9503"></word-count></counts><custom-meta-group><custom-meta><meta-name>cover-date</meta-name><meta-value>September 2018</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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