Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice
Details
Publication Year 2021-05-11, Volume 118, Issue #19, Page e2101918118
Journal Title
Proceedings of the National Academy of Sciences of the United States of America
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 angiotensin-converting 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 nanobody-Fc or as mixtures reduced viral loads by up to 10(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.
Publisher
NAS
Keywords
SARS-CoV-2; antiviral therapeutics; cryo-EM; crystallography; nanobodies; patent covering the nanobodies described in this manuscript.
WEHI Research Division(s)
Infectious Diseases And Immune Defence
PubMed ID
33893175
Open Access at Publisher's Site
https://doi.org/10.1073/pnas.2101918118
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2021-05-11 02:09:53
Last Modified: 2021-05-11 03:58:54
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