Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association
Jianhua Sui,Wenhui Li,Akikazu Murakami,Azaibi Tamin,Leslie J. Matthews,Swee Kee Wong,Michael Moore,Aimee St. Clair Tallarico,Mobolaji Olurinde,Hyeryun Choe,Larry J. Anderson,William J. Bellini,Michael Farzan,Wayne A. Marasco +13 more
TLDR
Data suggest that the 80R human monoclonal antibody may be a useful viral entry inhibitor for the emergency prophylaxis and treatment of SARS, and that the ACE2-binding site of S1 could be an attractive target for subunit vaccine and drug development.Abstract:
Effective prophylaxis and antiviral therapies are urgently needed in the event of reemergence of the highly contagious and often fatal severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) infection. We have identified eight recombinant human single-chain variable region fragments (scFvs) against the S1 domain of spike (S) protein of the SARS-CoV from two nonimmune human antibody libraries. One scFv 80R efficiently neutralized SARS-CoV and inhibited syncytia formation between cells expressing the S protein and those expressing the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2). Mapping of the 80R epitope showed it is located within the N-terminal 261–672 amino acids of S protein and is not glycosylation-dependent. 80R scFv competed with soluble ACE2 for association with the S1 domain and bound S1 with high affinity (equilibrium dissociation constant, Kd = 32.3 nM). A human IgG1 form of 80R bound S1 with a 20-fold higher affinity of 1.59 nM comparable to that of ACE2 (Kd = 1.70 nM), and neutralized virus 20-fold more efficiently than the 80R scFv. These data suggest that the 80R human monoclonal antibody may be a useful viral entry inhibitor for the emergency prophylaxis and treatment of SARS, and that the ACE2-binding site of S1 could be an attractive target for subunit vaccine and drug development.read more
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Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.
Alexandra C. Walls,Young-Jun Park,M. Alejandra Tortorici,M. Alejandra Tortorici,Abigail Wall,Andrew T. McGuire,Andrew T. McGuire,David Veesler +7 more
TL;DR: It is demonstrating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination, and it is shown that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of Sars- coV- 2 S and SARS S bind with similar affinities to human ACE2, correlating with the efficient spread of SATS among humans.
Journal ArticleDOI
Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus.
Wenhui Li,Michael Moore,Natalya Vasilieva,Jianhua Sui,Swee Kee Wong,Michael A. Berne,Mohan Somasundaran,John L. Sullivan,Katherine Luzuriaga,Thomas C. Greenough,Hyeryun Choe,Michael Farzan +11 more
TL;DR: It is found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells, indicating that ACE2 is a functional receptor for SARS-CoV.
Journal ArticleDOI
Structural basis of receptor recognition by SARS-CoV-2.
Jian Shang,Gang Ye,Ke Shi,Yushun Wan,Chuming Luo,Hideki Aihara,Qibin Geng,Ashley Auerbach,Fang Li +8 more
TL;DR: This study determines the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2 and sheds light on the structural features that increase its binding affinity to ACE2.
Journal ArticleDOI
The severe acute respiratory syndrome.
TL;DR: The concerted and coordinated response that contained SARS is a triumph for global public health and provides a new paradigm for the detection and control of future emerging infectious disease threats.
Journal ArticleDOI
Structure of SARS Coronavirus Spike Receptor-Binding Domain Complexed with Receptor
Fang Li,Wenhui Li,Wenhui Li,Michael Farzan,Michael Farzan,Stephen C. Harrison,Stephen C. Harrison +6 more
TL;DR: The structure of the RBD suggests ways to make truncated disulfide-stabilized RBD variants for use in the design of coronavirus vaccines.
References
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Journal ArticleDOI
Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus.
Wenhui Li,Michael Moore,Natalya Vasilieva,Jianhua Sui,Swee Kee Wong,Michael A. Berne,Mohan Somasundaran,John L. Sullivan,Katherine Luzuriaga,Thomas C. Greenough,Hyeryun Choe,Michael Farzan +11 more
TL;DR: It is found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells, indicating that ACE2 is a functional receptor for SARS-CoV.
Journal ArticleDOI
Identification of a novel coronavirus in patients with severe acute respiratory syndrome.
Christian Drosten,Stephan Günther,Wolfgang Preiser,Sylvie van der Werf,H. R. Brodt,Stephan Becker,Holger F. Rabenau,Marcus Panning,Larissa Kolesnikova,Ron A. M. Fouchier,Annemarie Berger,Ana-Maria Burguière,Jindrich Cinatl,Markus Eickmann,Nicolas Escriou,Klaus Grywna,Stefanie Kramme,Jean-Claude Manuguerra,Stefanie Müller,Volker Rickerts,Martin Stürmer,Simon Vieth,Hans-Dieter Klenk,Albert D. M. E. Osterhaus,Herbert Schmitz,Hans Wilhelm Doerr +25 more
TL;DR: The novel coronavirus might have a role in causing SARS and was detected in a variety of clinical specimens from patients with SARS but not in controls.
Journal ArticleDOI
A novel coronavirus associated with severe acute respiratory syndrome.
Thomas G. Ksiazek,Dean D. Erdman,Cynthia S. Goldsmith,Zaki,Teresa C. T. Peret,Shannon L. Emery,Suxiang Tong,Urbani C,James A. Comer,Wilina Lim,Pierre E. Rollin,Scott F. Dowell,Ai Ee Ling,Charles D. Humphrey,Wun-Ju Shieh,Jeannette Guarner,Christopher D. Paddock,Paul A. Rota,Barry S. Fields,Joseph L. DeRisi,Jyh-Yuan Yang,Nancy J. Cox,James M. Hughes,James W. LeDuc,William J. Bellini,Larry J. Anderson +25 more
TL;DR: A novel coronavirus is associated with this outbreak of severe acute respiratory syndrome, and the evidence indicates that this virus has an etiologic role in SARS.
Journal ArticleDOI
Characterization of a novel coronavirus associated with severe acute respiratory syndrome.
Paul A. Rota,M. Steven Oberste,Stephan S. Monroe,W. Allan Nix,Ray Campagnoli,Joseph P. Icenogle,Silvia Peñaranda,Bettina Bankamp,Kaija Maher,Min hsin Chen,Suxiong Tong,Azaibi Tamin,Luis Lowe,Michael Frace,Joseph L. DeRisi,Qi Chen,David Wang,Dean D. Erdman,Teresa C. T. Peret,Cara C. Burns,Thomas G. Ksiazek,Pierre E. Rollin,Anthony Sanchez,Stephanie L. Liffick,Brian P. Holloway,Josef Limor,Karen A. McCaustland,Mellissa Olsen-Rasmussen,Ron A. M. Fouchier,Stephan Günther,Albert Osterhaus,Christian Drosten,Mark A. Pallansch,Larry J. Anderson,William J. Bellini +34 more
TL;DR: Phylogenetic analyses and sequence comparisons showed that SARS-CoV is not closelyrelated to any of the previouslycharacterized coronaviruses.
Journal ArticleDOI
Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20
Reff Mitchell E,Kristin Carner,Karen S. Chambers,Paul Chinn,John E Leonard,Ron Raab,Roland A. Newman,Nabil Hanna,Darrell R Anderson +8 more
TL;DR: In vitro studies showed the ability of C2B8 to bind human C1q, mediate complement-dependent cell lysis of human B-lymphoid cell lines, and lyse human target cells through antibody-dependent cellular cytotoxicity and the possibility of using an "immunologically active" chimeric anti-CD20 antibody as an alternative approach in the treatment of B-cell lymphoma.
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