7WPH

SARS-CoV2 RBD bound to Fab06

Summary for 7WPH

• Entry DOI: 10.2210/pdb7wph/pdb
• Descriptor: Spike protein S1, FAB06 light chain, Fab06 heavy chain, ... (5 entities in total)
• Functional Keywords: sars-cov2 rbd, antibody, protein binding, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV,SARS-CoV-2); More
• Total number of polymer chains: 6
• Total formula weight: 155649.28

Authors

Lin, J.Q.,El Sahili, A.,Lescar, J. (deposition date: 2022-01-23, release date: 2022-03-30, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.89 Å)