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Pymm, P; Adair, A; Chan, LJ; Cooney, JP; Mordant, FL; Allison, CC; Lopez, E; Haycroft, ER; O'Neill, MT; Tan, LL; Dietrich, MH; Drew, D; Doerflinger, M; Dengler, MA; Scott, NE; Wheatley, AK; Gherardin, NA; Venugopal, H; Cromer, D; Davenport, MP; Pickering, R; Godfrey, DI; Purcell, DFJ; Kent, SJ; Chung, AW; Subbarao, K; Pellegrini, M; Glukhova, A; Tham, WH.
Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice.
Proc Natl Acad Sci U S A. 2021; 118(19): e2101918118 Doi: 10.1073/pnas.2101918118 [OPEN ACCESS]
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Co-authors Med Uni Graz: Dengler Michael
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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 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 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. Copyright © 2021 the Author(s). Published by PNAS.
Find related publications in this database (using NLM MeSH Indexing): Angiotensin-Converting Enzyme 2 - immunology; Animals -; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - pharmacology; Antibodies, Viral - immunology; Antibodies, Viral - pharmacology; COVID-19 - drug therapy; COVID-19 - immunology; Camelids, New World -; Humans -; Mice -; SARS-CoV-2 - immunology; Single-Domain Antibodies - immunology; Single-Domain Antibodies - pharmacology
Find related publications in this database (Keywords): SARS-CoV-2; nanobodies; crystallography; cryo-EM; antiviral therapeutics