7ZF9

SARS-CoV-2 Omicron BA.2 RBD in complex with COVOX-150 Fab (P21)

Summary for 7ZF9

• Entry DOI: 10.2210/pdb7zf9/pdb
• Related: 7ZF3 7ZF5 7ZF7 7ZF8
• Descriptor: COVOX-150 heavy chain, COVOX-150 light chain, Spike protein S1, ... (4 entities in total)
• Functional Keywords: sars-cov-2, omicron, ba.1, ba.2, rbd, antibody, fab, covox-150, viral protein/immune system, viral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 140245.13

Authors

Zhou, D.,Huo, J.,Ren, J.,Stuart, D.I. (deposition date: 2022-04-01, release date: 2022-06-01, Last modification date: 2024-10-23)

Primary citation

Nutalai, R.,Zhou, D.,Tuekprakhon, A.,Ginn, H.M.,Supasa, P.,Liu, C.,Huo, J.,Mentzer, A.J.,Duyvesteyn, H.M.E.,Dijokaite-Guraliuc, A.,Skelly, D.,Ritter, T.G.,Amini, A.,Bibi, S.,Adele, S.,Johnson, S.A.,Constantinides, B.,Webster, H.,Temperton, N.,Klenerman, P.,Barnes, E.,Dunachie, S.J.,Crook, D.,Pollard, A.J.,Lambe, T.,Goulder, P.,Paterson, N.G.,Williams, M.A.,Hall, D.R.,Mongkolsapaya, J.,Fry, E.E.,Dejnirattisai, W.,Ren, J.,Stuart, D.I.,Screaton, G.R.
Potent cross-reactive antibodies following Omicron breakthrough in vaccinees.
Cell, 185:2116-2131.e18, 2022

PubMed Abstract: Highly transmissible Omicron variants of SARS-CoV-2 currently dominate globally. Here, we compare neutralization of Omicron BA.1, BA.1.1, and BA.2. BA.2 RBD has slightly higher ACE2 affinity than BA.1 and slightly reduced neutralization by vaccine serum, possibly associated with its increased transmissibility. Neutralization differences between sub-lineages for mAbs (including therapeutics) mostly arise from variation in residues bordering the ACE2 binding site; however, more distant mutations S371F (BA.2) and R346K (BA.1.1) markedly reduce neutralization by therapeutic antibody Vir-S309. In-depth structure-and-function analyses of 27 potent RBD-binding mAbs isolated from vaccinated volunteers following breakthrough Omicron-BA.1 infection reveals that they are focused in two main clusters within the RBD, with potent right-shoulder antibodies showing increased prevalence. Selection and somatic maturation have optimized antibody potency in less-mutated epitopes and recovered potency in highly mutated epitopes. All 27 mAbs potently neutralize early pandemic strains, and many show broad reactivity with variants of concern.

PubMed: 35662412
DOI: 10.1016/j.cell.2022.05.014

Experimental method

X-RAY DIFFRACTION (3.25 Å)