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Basic Characteristics of Mutations
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Mutation Site
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N501Y |
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Mutation Site Sentence
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Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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RBD |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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COVID-19
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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33893175
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Title
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Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice
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Author
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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
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Journal
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Proceedings of the National Academy of Sciences of the United States of America
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Journal Info
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2021 May 11;118(19):e2101918118
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Abstract
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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.
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Sequence Data
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-
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