7NXA

Crystal structure of the receptor binding domain of SARS-CoV-2 B.1.351 variant Spike glycoprotein in complex with COVOX-222 and EY6A Fabs

Summary for 7NXA

• Entry DOI: 10.2210/pdb7nxa/pdb
• Related: 7NX6 7NX7 7NX8 7NX9
• Descriptor: EY6A Fab heavy chain, EY6A Fab light chain, Spike protein S1, ... (10 entities in total)
• Functional Keywords: sars-cov-2 b.1.1.7 variant, b.1.351 variant, p.1 variant, antibody, receptor-binding-domain, spike, neutralisation, viral protein/immune system, viral protein, immune system, viral protein-immune system complex
• Biological source: Homo sapiens; More
• Total number of polymer chains: 5
• Total formula weight: 120078.95

Authors

Zhou, D.,Ren, J.,Stuart, D. (deposition date: 2021-03-17, release date: 2021-04-07, Last modification date: 2024-10-16)

Primary citation

Dejnirattisai, W.,Zhou, D.,Supasa, P.,Liu, C.,Mentzer, A.J.,Ginn, H.M.,Zhao, Y.,Duyvesteyn, H.M.E.,Tuekprakhon, A.,Nutalai, R.,Wang, B.,Lopez-Camacho, C.,Slon-Campos, J.,Walter, T.S.,Skelly, D.,Costa Clemens, S.A.,Naveca, F.G.,Nascimento, V.,Nascimento, F.,Fernandes da Costa, C.,Resende, P.C.,Pauvolid-Correa, A.,Siqueira, M.M.,Dold, C.,Levin, R.,Dong, T.,Pollard, A.J.,Knight, J.C.,Crook, D.,Lambe, T.,Clutterbuck, E.,Bibi, S.,Flaxman, A.,Bittaye, M.,Belij-Rammerstorfer, S.,Gilbert, S.C.,Carroll, M.W.,Klenerman, P.,Barnes, E.,Dunachie, S.J.,Paterson, N.G.,Williams, M.A.,Hall, D.R.,Hulswit, R.J.G.,Bowden, T.A.,Fry, E.E.,Mongkolsapaya, J.,Ren, J.,Stuart, D.I.,Screaton, G.R.
Antibody evasion by the P.1 strain of SARS-CoV-2.
Cell, 184:2939-, 2021

PubMed Abstract: Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations, including P.1 from Brazil, B.1.351 from South Africa, and B.1.1.7 from the UK (12, 10, and 9 changes in the spike, respectively). All have mutations in the ACE2 binding site, with P.1 and B.1.351 having a virtually identical triplet (E484K, K417N/T, and N501Y), which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine-induced antibody responses than B.1.351, suggesting that changes outside the receptor-binding domain (RBD) impact neutralization. Monoclonal antibody (mAb) 222 neutralizes all three variants despite interacting with two of the ACE2-binding site mutations. We explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.

PubMed: 33852911
DOI: 10.1016/j.cell.2021.03.055

Experimental method

X-RAY DIFFRACTION (2.5 Å)