7P7A

SARS-CoV-2 spike protein in complex with sybody#68 in a 2up/1flexible conformation

7P7A の概要

• エントリーDOI: 10.2210/pdb7p7a/pdb
• EMDBエントリー: 12085
• 分子名称: Spike glycoprotein, sybody#68, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: sars-cov-2 spike protein sybody, viral protein
• 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: 5
• 化学式量合計: 467968.98

構造登録者

Walter, J.D.,Hutter, C.A.J.,Garaeva, A.A.,Scherer, M.,Zimmermann, I.,Wyss, M.,Rheinberger, J.,Ruedin, Y.,Earp, J.C.,Egloff, P.,Sorgenfrei, M.,Huerlimann, L.M.,Gonda, I.,Meier, G.,Remm, S.,Thavarasah, S.,Zimmer, G.,Slotboom, D.J.,Paulino, C.,Plattet, P.,Seeger, M.A. (登録日: 2021-07-19, 公開日: 2021-08-04, 最終更新日: 2024-11-13)

主引用文献

Walter, J.D.,Scherer, M.,Hutter, C.A.J.,Garaeva, A.A.,Zimmermann, I.,Wyss, M.,Rheinberger, J.,Ruedin, Y.,Earp, J.C.,Egloff, P.,Sorgenfrei, M.,Hurlimann, L.M.,Gonda, I.,Meier, G.,Remm, S.,Thavarasah, S.,van Geest, G.,Bruggmann, R.,Zimmer, G.,Slotboom, D.J.,Paulino, C.,Plattet, P.,Seeger, M.A.
Biparatopic sybodies neutralize SARS-CoV-2 variants of concern and mitigate drug resistance.
Embo Rep., 23:e54199-e54199, 2022

PubMed Abstract: The ongoing COVID-19 pandemic represents an unprecedented global health crisis. Here, we report the identification of a synthetic nanobody (sybody) pair, Sb#15 and Sb#68, that can bind simultaneously to the SARS-CoV-2 spike RBD and efficiently neutralize pseudotyped and live viruses by interfering with ACE2 interaction. Cryo-EM confirms that Sb#15 and Sb#68 engage two spatially discrete epitopes, influencing rational design of bispecific and tri-bispecific fusion constructs that exhibit up to 100- and 1,000-fold increase in neutralization potency, respectively. Cryo-EM of the sybody-spike complex additionally reveals a novel up-out RBD conformation. While resistant viruses emerge rapidly in the presence of single binders, no escape variants are observed in the presence of the bispecific sybody. The multivalent bispecific constructs further increase the neutralization potency against globally circulating SARS-CoV-2 variants of concern. Our study illustrates the power of multivalency and biparatopic nanobody fusions for the potential development of therapeutic strategies that mitigate the emergence of new SARS-CoV-2 escape mutants.

PubMed: 35253970
DOI: 10.15252/embr.202154199

実験手法

ELECTRON MICROSCOPY (4.76 Å)