Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice.

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Publisher: National Academy of Sciences
Document Type: Report
Length: 12,197 words
Lexile Measure: 1560L

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Abstract :

Neutralizing antibodies are important for immunity against SARS-CoV-2 and as therapeutics for the prevention and treatment of COVID-19. Here, we identified high-affinity nanobodies from alpacas immunized with coronavirus spike and receptor-binding domains (RBD) that disrupted RBD engagement with the human receptor angiotensinconverting enzyme 2 (ACE2) and potently neutralized SARS-CoV-2. Epitope mapping, X-ray crystallography, and cryo-electron microscopy revealed two distinct antigenic sites and showed two neutralizing nanobodies from different epitope classes bound simultaneously to the spike trimer. Nanobody-Fc fusions of the four most potent nanobodies blocked ACE2 engagement with RBD variants present in human populations and potently neutralized both wild-type SARS-CoV-2 and the N501Y D614G variant at concentrations as low as 0.1 nM. Prophylactic administration of either single nanobodyFc or as mixtures reduced viral loads by up to [10.sup.4]-fold in mice infected with the N501Y D614G SARS-CoV-2 virus. These results suggest a role for nanobody-Fc fusions as prophylactic agents against SARS-CoV-2. SARS-CoV-2 | nanobodies | crystallography | cryo-EM | antiviral therapeutics

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Gale Document Number: GALE|A662784541