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10.1126/science.abf4830

http://scihub22266oqcxt.onion/10.1126/science.abf4830
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33495307!7963221!33495307
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suck abstract from ncbi


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pmid33495307      Science 2021 ; 371 (6531): 823-829
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  • Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody #MMPMID33495307
  • Rappazzo CG; Tse LV; Kaku CI; Wrapp D; Sakharkar M; Huang D; Deveau LM; Yockachonis TJ; Herbert AS; Battles MB; O'Brien CM; Brown ME; Geoghegan JC; Belk J; Peng L; Yang L; Hou Y; Scobey TD; Burton DR; Nemazee D; Dye JM; Voss JE; Gunn BM; McLellan JS; Baric RS; Gralinski LE; Walker LM
  • Science 2021[Feb]; 371 (6531): 823-829 PMID33495307show ga
  • The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains and neutralizes representative epidemic sarbecoviruses with high potency. Structural and biochemical studies demonstrate that ADG-2 employs a distinct angle of approach to recognize a highly conserved epitope that overlaps the receptor binding site. In immunocompetent mouse models of SARS and COVID-19, prophylactic administration of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate against clade 1 sarbecoviruses.
  • |Angiotensin-Converting Enzyme 2/metabolism[MESH]
  • |Animals[MESH]
  • |Antibodies, Monoclonal/genetics/*immunology/metabolism[MESH]
  • |Antibodies, Viral/genetics/*immunology/metabolism[MESH]
  • |Antibody Affinity[MESH]
  • |Betacoronavirus/*immunology[MESH]
  • |Binding Sites[MESH]
  • |Binding Sites, Antibody[MESH]
  • |Broadly Neutralizing Antibodies/genetics/*immunology/metabolism[MESH]
  • |COVID-19 Serotherapy[MESH]
  • |COVID-19/prevention & control/therapy[MESH]
  • |Cell Surface Display Techniques[MESH]
  • |Directed Molecular Evolution[MESH]
  • |Epitopes/immunology[MESH]
  • |Humans[MESH]
  • |Immunization, Passive[MESH]
  • |Immunoglobulin Fc Fragments/immunology[MESH]
  • |Mice[MESH]
  • |Mice, Inbred BALB C[MESH]
  • |Protein Domains[MESH]
  • |Protein Engineering[MESH]
  • |Receptors, Coronavirus/metabolism[MESH]
  • |SARS-CoV-2/*immunology[MESH]
  • |Severe Acute Respiratory Syndrome/immunology/prevention & control/therapy[MESH]
  • |Severe acute respiratory syndrome-related coronavirus/immunology[MESH]


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