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

Authors :
Pymm, Phillip
Adair, Amy
Li-Jin Chan
Cooney, James P.
Mordant, Francesca L.
Allison, Cody C.
Lopez, Ester
Haycroft, Ebene R.
O'Neill, Matthew T.
Li Lynn Tan
Dietrich, Melanie H.
Drew, Damien
Gherardin, Nicholas A.
Venugopal, Hariprasad
Cromer, Deborah
Davenport, Miles P.
Pickering, Raelene
Godfrey, Dale I.
Purcell, Damian F. J.
Kent, Stephen J.
Source :
Proceedings of the National Academy of Sciences of the United States of America. 5/11/2021, Vol. 118 Issue 19, p1-12. 12p.
Publication Year :
2021

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 nanobody-Fc or as mixtures reduced viral loads by up to 104-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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00278424
Volume :
118
Issue :
19
Database :
Academic Search Index
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Publication Type :
Academic Journal
Accession number :
150423285
Full Text :
https://doi.org/10.1073/pnas.2101918118