7WPV

Fab14 - a SARS-CoV2 RBD neutralising antibody

7WPV の概要

• エントリーDOI: 10.2210/pdb7wpv/pdb
• 分子名称: Fab14 light chain, Fab14 heavy chain (3 entities in total)
• 機能のキーワード: sars-cov2 rbd neutralising antibody, protein binding, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48102.32

構造登録者

Lin, J.Q.,El Sahili, A.,Lescar, J. (登録日: 2022-01-24, 公開日: 2022-03-30, 最終更新日: 2024-11-06)

主引用文献

Ku, Z.,Xie, X.,Lin, J.,Gao, P.,Wu, B.,El Sahili, A.,Su, H.,Liu, Y.,Ye, X.,Tan, E.Y.,Li, X.,Fan, X.,Goh, B.C.,Xiong, W.,Boyd, H.,Muruato, A.E.,Deng, H.,Xia, H.,Zou, J.,Kalveram, B.K.,Menachery, V.D.,Zhang, N.,Lescar, J.,Shi, P.Y.,An, Z.
Engineering SARS-CoV-2 specific cocktail antibodies into a bispecific format improves neutralizing potency and breadth.
Nat Commun, 13:5552-5552, 2022

PubMed Abstract: One major limitation of neutralizing antibody-based COVID-19 therapy is the requirement of costly cocktails to reduce emergence of antibody resistance. Here we engineer two bispecific antibodies (bsAbs) using distinct designs and compared them with parental antibodies and their cocktail. Single molecules of both bsAbs block the two epitopes targeted by parental antibodies on the receptor-binding domain (RBD). However, bsAb with the IgG-(scFv) design (14-H-06) but not the CrossMAb design (14-crs-06) shows increased antigen-binding and virus-neutralizing activities against multiple SARS-CoV-2 variants as well as increased breadth of neutralizing activity compared to the cocktail. X-ray crystallography and cryo-EM reveal distinct binding models for individual cocktail antibodies, and computational simulations suggest higher inter-spike crosslinking potentials by 14-H-06 than 14-crs-06. In mouse models of infections by SARS-CoV-2 and multiple variants, 14-H-06 exhibits higher or equivalent therapeutic efficacy than the cocktail. Rationally engineered bsAbs represent a cost-effective alternative to antibody cocktails and a promising strategy to improve potency and breadth.

PubMed: 36138032
DOI: 10.1038/s41467-022-33284-y

実験手法

X-RAY DIFFRACTION (2.46 Å)