A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2.

Nature
Rui ShiJinghua Yan

Abstract

An outbreak of coronavirus disease 2019 (COVID-19)1-3, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)4, has spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.

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Datasets Mentioned

BETA
BAJ21180
JX869050

Methods Mentioned

BETA
fluorescence-activated cell sorting
surface plasmon resonance
PCR
light microscopy
X-ray
surface
biolayer interferometry
gel filtration
flow cytometry
biosensor

Clinical Trials Mentioned

NCT04292340
NCT04327349
NCT04321421

Software Mentioned

FlowJo
Pymol
MolProbity
Coot
Octet
Phaser
Phenix
BIAevaluation
GraphPad Prism

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