8EOO

Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing human antibodies WRAIR-2063 and WRAIR-2151

8EOO の概要

• エントリーDOI: 10.2210/pdb8eoo/pdb
• 分子名称: WRAIR-2151 antibody Fab heavy chain, WRAIR-2151 antibody Fab light chain, Spike protein S1, ... (8 entities in total)
• 機能のキーワード: viral protein, immune system, complex, human antibodies
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 237870.62

構造登録者

Jensen, J.L.,Sankhala, R.S.,Joyce, M.G. (登録日: 2022-10-03, 公開日: 2023-06-14, 最終更新日: 2023-10-25)

主引用文献

Jensen, J.L.,Sankhala, R.S.,Dussupt, V.,Bai, H.,Hajduczki, A.,Lal, K.G.,Chang, W.C.,Martinez, E.J.,Peterson, C.E.,Golub, E.S.,Rees, P.A.,Mendez-Rivera, L.,Zemil, M.,Kavusak, E.,Mayer, S.V.,Wieczorek, L.,Kannan, S.,Doranz, B.J.,Davidson, E.,Yang, E.S.,Zhang, Y.,Chen, M.,Choe, M.,Wang, L.,Gromowski, G.D.,Koup, R.A.,Michael, N.L.,Polonis, V.R.,Rolland, M.,Modjarrad, K.,Krebs, S.J.,Joyce, M.G.
Targeting the Spike Receptor Binding Domain Class V Cryptic Epitope by an Antibody with Pan-Sarbecovirus Activity.
J.Virol., 97:e0159622-e0159622, 2023

PubMed Abstract: Novel therapeutic monoclonal antibodies (MAbs) must accommodate comprehensive breadth of activity against diverse sarbecoviruses and high neutralization potency to overcome emerging variants. Here, we report the crystal structure of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD) in complex with MAb WRAIR-2063, a moderate-potency neutralizing antibody with exceptional sarbecovirus breadth, that targets the highly conserved cryptic class V epitope. This epitope overlaps substantially with the spike protein N-terminal domain (NTD) -interacting region and is exposed only when the spike is in the open conformation, with one or more RBDs accessible. WRAIR-2063 binds the RBD of SARS-CoV-2 WA-1, all variants of concern (VoCs), and clade 1 to 4 sarbecoviruses with high affinity, demonstrating the conservation of this epitope and potential resiliency against variation. We compare structural features of additional class V antibodies with their reported neutralization capacity to further explore the utility of the class V epitope as a pan-sarbecovirus vaccine and therapeutic target. Characterization of MAbs against SARS-CoV-2, elicited through vaccination or natural infection, has provided vital immunotherapeutic options for curbing the COVID-19 pandemic and has supplied critical insights into SARS-CoV-2 escape, transmissibility, and mechanisms of viral inactivation. Neutralizing MAbs that target the RBD but do not block ACE2 binding are of particular interest because the epitopes are well conserved within sarbecoviruses and MAbs targeting this area demonstrate cross-reactivity. The class V RBD-targeted MAbs localize to an invariant site of vulnerability, provide a range of neutralization potency, and exhibit considerable breadth against divergent sarbecoviruses, with implications for vaccine and therapeutic development.

PubMed: 37395646
DOI: 10.1128/jvi.01596-22

実験手法

X-RAY DIFFRACTION (2.77 Å)