RT Journal Article
SR Electronic
T1 Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.26.010165
DO 10.1101/2020.03.26.010165
A1 Daniel Wrapp
A1 Dorien De Vlieger
A1 Kizzmekia S. Corbett
A1 Gretel M. Torres
A1 Wander Van Breedam
A1 Kenny Roose
A1 Loes van Schie
A1 VIB-CMB COVID-19 Response Team
A1 Markus Hoffmann
A1 Stefan Pöhlmann
A1 Barney S. Graham
A1 Nico Callewaert
A1 Bert Schepens
A1 Xavier Saelens
A1 Jason S. McLellan
YR 2020
UL http://biorxiv.org/content/early/2020/03/28/2020.03.26.010165.abstract
AB The 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.