7tas
From Proteopedia
SARS-CoV-2 spike in complex with the S2K146 neutralizing antibody Fab fragment (local refinement of the RBD and S2K146)
Structural highlights
Publication Abstract from PubMedUnderstanding broadly neutralizing sarbecovirus antibody responses is key to developing countermeasures against SARS-CoV-2 variants and future zoonotic sarbecoviruses. We describe the isolation and characterization of a human monoclonal antibody, designated S2K146, that broadly neutralizes viruses belonging to SARS-CoV- and SARS-CoV-2-related sarbecovirus clades which use ACE2 as an entry receptor. Structural and functional studies show that most of the virus residues that directly bind S2K146 are also involved in binding to ACE2. This allows the antibody to potently inhibit receptor attachment. S2K146 protects against SARS-CoV-2 Beta challenge in hamsters and viral passaging experiments reveal a high barrier for emergence of escape mutants, making it a good candidate for clinical development. The conserved ACE2-binding residues present a site of vulnerability that might be leveraged for developing vaccines eliciting broad sarbecovirus immunity. Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry.,Park YJ, De Marco A, Starr TN, Liu Z, Pinto D, Walls AC, Zatta F, Zepeda SK, Bowen JE, Sprouse KR, Joshi A, Giurdanella M, Guarino B, Noack J, Abdelnabi R, Foo SC, Rosen LE, Lempp FA, Benigni F, Snell G, Neyts J, Whelan SPJ, Virgin HW, Bloom JD, Corti D, Pizzuto MS, Veesler D Science. 2022 Jan 28;375(6579):449-454. doi: 10.1126/science.abm8143. Epub 2022 , Jan 6. PMID:34990214[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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