scholarly journals Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies

Author(s):  
Daniel Wrapp ◽  
Dorien De Vlieger ◽  
Kizzmekia S. Corbett ◽  
Gretel M. Torres ◽  
Wander Van Breedam ◽  
...  

ABSTRACTThe pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV-1) and COVID-19 coronavirus (SARS-CoV-2) have all emerged into the human population with devastating consequences. These viruses make use of a large envelope protein called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins play, they represent a vulnerable target for the development of therapeutics to combat these highly pathogenic coronaviruses. Here, we describe the isolation and characterization of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs are capable of potently neutralizing MERS-CoV or SARS-CoV-1 S pseudotyped viruses. The crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs block receptor binding. We also show cross-reactivity between the SARS-CoV-1 S-directed VHH and SARS-CoV-2 S, and demonstrate that this cross-reactive VHH is capable of neutralizing SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc-fusion. These data provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronavirus outbreaks.

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Greg Hussack ◽  
Shalini Raphael ◽  
Michael J. Lowden ◽  
Kevin A. Henry

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiaozhen Ye ◽  
Shan Lu ◽  
Kevin D. Corbett

The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is the most severe public health event of the twenty-first century. While effective vaccines against SARS-CoV-2 have been developed, there remains an urgent need for diagnostics to quickly and accurately detect infections. Antigen tests, particularly those that detect the abundant SARS-CoV-2 Nucleocapsid protein, are a proven method for detecting active SARS-CoV-2 infections. Here we report high-resolution crystal structures of three llama-derived single-domain antibodies that bind the SARS-CoV-2 Nucleocapsid protein with high affinity. Each antibody recognizes a specific folded domain of the protein, with two antibodies recognizing the N-terminal RNA binding domain and one recognizing the C-terminal dimerization domain. The two antibodies that recognize the RNA binding domain affect both RNA binding affinity and RNA-mediated phase separation of the Nucleocapsid protein. All three antibodies recognize highly conserved surfaces on the Nucleocapsid protein, suggesting that they could be used to develop affordable diagnostic tests to detect all circulating SARS-CoV-2 variants.


Immunology ◽  
2016 ◽  
Vol 149 (1) ◽  
pp. 111-121 ◽  
Author(s):  
Roeland Lameris ◽  
Renée C. G. de Bruin ◽  
Paul M. P. van Bergen en Henegouwen ◽  
Henk M. Verheul ◽  
Sonja Zweegman ◽  
...  

2016 ◽  
Vol 78 ◽  
pp. 146-154 ◽  
Author(s):  
Jinny L. Liu ◽  
Dan Zabetakis ◽  
Ellen R. Goldman ◽  
George P. Anderson

mAbs ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 1708030
Author(s):  
Bharathikumar Vellalore Maruthachalam ◽  
Adam Zwolak ◽  
Xiefan Lin-Schmidt ◽  
Edward Keough ◽  
Ninkka Tamot ◽  
...  

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