tetano
Editor, Senior Moderator
Cell. 2020 Apr 29. pii: S0092-8674(20)30494-3. doi: 10.1016/j.cell.2020.04.031. [Epub ahead of print]
Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies.
Wrapp D[SUP]1[/SUP], De Vlieger D[SUP]2[/SUP], Corbett KS[SUP]3[/SUP], Torres GM[SUP]4[/SUP], Wang N[SUP]1[/SUP], Van Breedam W[SUP]5[/SUP], Roose K[SUP]5[/SUP], van Schie L[SUP]5[/SUP]; VIB-CMB COVID-19 Response Team, Hoffmann M[SUP]6[/SUP], P?hlmann S[SUP]7[/SUP], Graham BS[SUP]3[/SUP], Callewaert N[SUP]5[/SUP], Schepens B[SUP]8[/SUP], Saelens X[SUP]9[/SUP], McLellan JS[SUP]10[/SUP].
Author information
Abstract
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.
Copyright ? 2020 Elsevier Inc. All rights reserved.
KEYWORDS:
COVID-19; MERS; SARS; SARS-CoV-2; nanobody
PMID:32375025DOI:10.1016/j.cell.2020.04.031
Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies.
Wrapp D[SUP]1[/SUP], De Vlieger D[SUP]2[/SUP], Corbett KS[SUP]3[/SUP], Torres GM[SUP]4[/SUP], Wang N[SUP]1[/SUP], Van Breedam W[SUP]5[/SUP], Roose K[SUP]5[/SUP], van Schie L[SUP]5[/SUP]; VIB-CMB COVID-19 Response Team, Hoffmann M[SUP]6[/SUP], P?hlmann S[SUP]7[/SUP], Graham BS[SUP]3[/SUP], Callewaert N[SUP]5[/SUP], Schepens B[SUP]8[/SUP], Saelens X[SUP]9[/SUP], McLellan JS[SUP]10[/SUP].
Author information
Abstract
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.
Copyright ? 2020 Elsevier Inc. All rights reserved.
KEYWORDS:
COVID-19; MERS; SARS; SARS-CoV-2; nanobody
PMID:32375025DOI:10.1016/j.cell.2020.04.031