7N4M

Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing human antibody WRAIR-2151.

Summary for 7N4M

• Entry DOI: 10.2210/pdb7n4m/pdb
• Descriptor: WRAIR-2151 antibody Fab heavy chain, Spike protein S1, WRAIR-2151 antibody Fab light chain, ... (4 entities in total)
• Functional Keywords: neutralizing antibody, sars-cov-2, wrair-2151, receptor binding domain, antiviral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 70723.46

Authors

Sankhala, R.S.,Joyce, M.G. (deposition date: 2021-06-04, release date: 2021-11-10, Last modification date: 2024-10-30)

Primary citation

Dussupt, V.,Sankhala, R.S.,Mendez-Rivera, L.,Townsley, S.M.,Schmidt, F.,Wieczorek, L.,Lal, K.G.,Donofrio, G.C.,Tran, U.,Jackson, N.D.,Zaky, W.I.,Zemil, M.,Tritsch, S.R.,Chen, W.H.,Martinez, E.J.,Ahmed, A.,Choe, M.,Chang, W.C.,Hajduczki, A.,Jian, N.,Peterson, C.E.,Rees, P.A.,Rutkowska, M.,Slike, B.M.,Selverian, C.N.,Swafford, I.,Teng, I.T.,Thomas, P.V.,Zhou, T.,Smith, C.J.,Currier, J.R.,Kwong, P.D.,Rolland, M.,Davidson, E.,Doranz, B.J.,Mores, C.N.,Hatziioannou, T.,Reiley, W.W.,Bieniasz, P.D.,Paquin-Proulx, D.,Gromowski, G.D.,Polonis, V.R.,Michael, N.L.,Modjarrad, K.,Joyce, M.G.,Krebs, S.J.
Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations.
Nat.Immunol., 22:1503-1514, 2021

PubMed Abstract: Prevention of viral escape and increased coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern require therapeutic monoclonal antibodies (mAbs) targeting multiple sites of vulnerability on the coronavirus spike glycoprotein. Here we identify several potent neutralizing antibodies directed against either the N-terminal domain (NTD) or the receptor-binding domain (RBD) of the spike protein. Administered in combinations, these mAbs provided low-dose protection against SARS-CoV-2 infection in the K18-human angiotensin-converting enzyme 2 mouse model, using both neutralization and Fc effector antibody functions. The RBD mAb WRAIR-2125, which targets residue F486 through a unique heavy-chain and light-chain pairing, demonstrated potent neutralizing activity against all major SARS-CoV-2 variants of concern. In combination with NTD and other RBD mAbs, WRAIR-2125 also prevented viral escape. These data demonstrate that NTD/RBD mAb combinations confer potent protection, likely leveraging complementary mechanisms of viral inactivation and clearance.

PubMed: 34716452
DOI: 10.1038/s41590-021-01068-z

Experimental method

X-RAY DIFFRACTION (3.79 Å)