7R7N

SARS-CoV-2 spike in complex with the S2D106 neutralizing antibody Fab fragment (local refinement of the RBD and S2D106)

Summary for 7R7N

• Entry DOI: 10.2210/pdb7r7n/pdb
• EMDB information: 24299
• Descriptor: S2D106 FAB heavy chain, Spike glycoprotein, S2D106 FAB light chain, ... (4 entities in total)
• Functional Keywords: sars-cov-2, covid-19, spike glycoprotein, fusion protein, neutralizing antibodies, structural genomics, seattle structural genomics center for infectious disease, ssgcid, inhibitor, viral 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: 167988.71

Authors

Park, Y.J.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2021-06-25, release date: 2021-07-21, Last modification date: 2024-11-06)

Primary citation

Starr, T.N.,Czudnochowski, N.,Liu, Z.,Zatta, F.,Park, Y.J.,Addetia, A.,Pinto, D.,Beltramello, M.,Hernandez, P.,Greaney, A.J.,Marzi, R.,Glass, W.G.,Zhang, I.,Dingens, A.S.,Bowen, J.E.,Tortorici, M.A.,Walls, A.C.,Wojcechowskyj, J.A.,De Marco, A.,Rosen, L.E.,Zhou, J.,Montiel-Ruiz, M.,Kaiser, H.,Dillen, J.R.,Tucker, H.,Bassi, J.,Silacci-Fregni, C.,Housley, M.P.,di Iulio, J.,Lombardo, G.,Agostini, M.,Sprugasci, N.,Culap, K.,Jaconi, S.,Meury, M.,Dellota Jr., E.,Abdelnabi, R.,Foo, S.C.,Cameroni, E.,Stumpf, S.,Croll, T.I.,Nix, J.C.,Havenar-Daughton, C.,Piccoli, L.,Benigni, F.,Neyts, J.,Telenti, A.,Lempp, F.A.,Pizzuto, M.S.,Chodera, J.D.,Hebner, C.M.,Virgin, H.W.,Whelan, S.P.J.,Veesler, D.,Corti, D.,Bloom, J.D.,Snell, G.
SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape.
Nature, 597:97-102, 2021

PubMed Abstract: An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape, have activity against diverse sarbecoviruses, and be highly protective through viral neutralization and effector functions. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E12) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics.

PubMed: 34261126
DOI: 10.1038/s41586-021-03807-6

Experimental method

ELECTRON MICROSCOPY (3.95 Å)