Mar 28, 2020

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

BioRxiv : the Preprint Server for Biology
Stephan HeermannJason S McLellan

Abstract

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 betaco...Continue Reading

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Mentioned in this Paper

Vertebrates
Pigment Epithelium
Anatomical Layer
Epithelium of Lens
Eye Morphogenesis
Collagenosis, Familial Reactive Perforating
Epithelium
Eye Development
Bone Morphogenetic Proteins
Entire Optic Cup

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