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  • Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain #MMPMID34855508
  • Nabel KG; Clark SA; Shankar S; Pan J; Clark LE; Yang P; Coscia A; McKay LGA; Varnum HH; Brusic V; Tolan NV; Zhou G; Desjardins M; Turbett SE; Kanjilal S; Sherman AC; Dighe A; LaRocque RC; Ryan ET; Tylek C; Cohen-Solal JF; Darcy AT; Tavella D; Clabbers A; Fan Y; Griffiths A; Correia IR; Seagal J; Baden LR; Charles RC; Abraham J
  • Science 2022[Jan]; 375 (6578): eabl6251 PMID34855508show ga
  • Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we evaluate the consequences of further viral evolution. We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans.
  • |*Immune Evasion[MESH]
  • |Angiotensin-Converting Enzyme 2/chemistry/metabolism[MESH]
  • |Antibodies, Neutralizing/*immunology[MESH]
  • |Antibodies, Viral/*immunology[MESH]
  • |BNT162 Vaccine/immunology[MESH]
  • |Betacoronavirus/immunology[MESH]
  • |COVID-19/immunology/virology[MESH]
  • |Cross Reactions[MESH]
  • |Cryoelectron Microscopy[MESH]
  • |Crystallography, X-Ray[MESH]
  • |Epitopes[MESH]
  • |Evolution, Molecular[MESH]
  • |Humans[MESH]
  • |Models, Molecular[MESH]
  • |Mutation[MESH]
  • |Polysaccharides/analysis[MESH]
  • |Protein Binding[MESH]
  • |Protein Domains[MESH]
  • |Receptors, Coronavirus/chemistry/metabolism[MESH]
  • |SARS-CoV-2/genetics/*immunology[MESH]
  • |Spike Glycoprotein, Coronavirus/*chemistry/genetics/*immunology[MESH]
  • |Viral Pseudotyping[MESH]

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  • suck abstract from ncbi

    eabl6251 6578.375 2022