[PDF][PDF] Structural basis for potent neutralization of betacoronaviruses by single-domain camelid antibodies
Cell, 2020•cell.com
Coronaviruses 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. Here, we describe
the isolation of single-domain antibodies (VHHs) from a llama immunized with prefusion-
stabilized coronavirus spikes. These VHHs neutralize MERS-CoV or SARS-CoV-1 S
pseudotyped viruses, respectively. Crystal structures of these VHHs bound to their …
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. Here, we describe
the isolation of single-domain antibodies (VHHs) from a llama immunized with prefusion-
stabilized coronavirus spikes. These VHHs neutralize MERS-CoV or SARS-CoV-1 S
pseudotyped viruses, respectively. Crystal structures of these VHHs bound to their …
Summary
Coronaviruses 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. Here, we describe the isolation of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs neutralize MERS-CoV or SARS-CoV-1 S pseudotyped viruses, respectively. Crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs interfere with 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 neutralizes 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.
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