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National Academy of Sciences, Proceedings of the National Academy of Sciences, 19(118), 2021

DOI: 10.1073/pnas.2101918118

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

Journal article published in 2021 by Phillip Pymm ORCID, Amy Adair ORCID, Li-Jin Chan ORCID, James P. Cooney ORCID, Francesca L. Mordant ORCID, Cody C. Allison, Ester Lopez ORCID, Ebene R. Haycroft, Matthew T. O’Neill ORCID, Li Lynn Tan ORCID, Melanie H. Dietrich ORCID, Damien Drew, Marcel Doerflinger ORCID, Michael A. Dengler ORCID, Nichollas E. Scott ORCID and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Significance Neutralizing antibodies are important for immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and as therapeutics for the prevention and treatment of COVID-19. We identified high-affinity nanobodies against SARS-CoV-2 receptor-binding domain and found that nanobody cocktails consisting of two noncompeting nanobodies were able to block ACE2 engagement with RBD variants present in human populations and potently neutralize both wild-type SARS-CoV-2 and the N501Y D614G variant at low concentrations. Prophylactic administration of nanobody cocktails reduced viral loads in mice infected with the N501Y D614G SARS-CoV-2 virus, showing that nanobody cocktails are useful as prophylactic agents against SARS-CoV-2.