7RAL

SARS-CoV-2 S bound to S2X259 Fab (local refinement of the RBD/S2X259 variable domains)

7RAL の概要

• エントリーDOI: 10.2210/pdb7ral/pdb
• EMDBエントリー: 24365
• 分子名称: S2X259 Fab heavy chain, S2X259 Fab light chain, Spike glycoprotein, ... (4 entities in total)
• 機能のキーワード: sars-cov-2, spike glycoprotein, fab s2x259, viral protein, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 168110.86

構造登録者

Veesler, D.,Tortorici, M.A.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (登録日: 2021-07-01, 公開日: 2021-08-04, 最終更新日: 2025-03-19)

主引用文献

Tortorici, M.A.,Czudnochowski, N.,Starr, T.N.,Marzi, R.,Walls, A.C.,Zatta, F.,Bowen, J.E.,Jaconi, S.,Di Iulio, J.,Wang, Z.,De Marco, A.,Zepeda, S.K.,Pinto, D.,Liu, Z.,Beltramello, M.,Bartha, I.,Housley, M.P.,Lempp, F.A.,Rosen, L.E.,Dellota Jr., E.,Kaiser, H.,Montiel-Ruiz, M.,Zhou, J.,Addetia, A.,Guarino, B.,Culap, K.,Sprugasci, N.,Saliba, C.,Vetti, E.,Giacchetto-Sasselli, I.,Fregni, C.S.,Abdelnabi, R.,Foo, S.C.,Havenar-Daughton, C.,Schmid, M.A.,Benigni, F.,Cameroni, E.,Neyts, J.,Telenti, A.,Virgin, H.W.,Whelan, S.P.J.,Snell, G.,Bloom, J.D.,Corti, D.,Veesler, D.,Pizzuto, M.S.
Broad sarbecovirus neutralization by a human monoclonal antibody.
Nature, 597:103-108, 2021

PubMed Abstract: The recent emergence of SARS-CoV-2 variants of concern and the recurrent spillovers of coronaviruses into the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here we describe a human monoclonal antibody designated S2X259, which recognizes a highly conserved cryptic epitope of the receptor-binding domain and cross-reacts with spikes from all clades of sarbecovirus. S2X259 broadly neutralizes spike-mediated cell entry of SARS-CoV-2, including variants of concern (B.1.1.7, B.1.351, P.1, and B.1.427/B.1.429), as well as a wide spectrum of human and potentially zoonotic sarbecoviruses through inhibition of angiotensin-converting enzyme 2 (ACE2) binding to the receptor-binding domain. Furthermore, deep-mutational scanning and in vitro escape selection experiments demonstrate that S2X259 possesses an escape profile that is limited to a single substitution, G504D. We show that prophylactic and therapeutic administration of S2X259 protects Syrian hamsters (Mesocricetus auratus) against challenge with the prototypic SARS-CoV-2 and the B.1.351 variant of concern, which suggests that this monoclonal antibody is a promising candidate for the prevention and treatment of emergent variants and zoonotic infections. Our data reveal a key antigenic site that is targeted by broadly neutralizing antibodies and will guide the design of vaccines that are effective against all sarbecoviruses.

PubMed: 34280951
DOI: 10.1038/s41586-021-03817-4

実験手法

ELECTRON MICROSCOPY (3.7 Å)