7K3Q

An ultra-potent human neutralizing antibody locks the SARS-CoV-2 spike in the closed conformation

Summary for 7K3Q

• Entry DOI: 10.2210/pdb7k3q/pdb
• Descriptor: Fab fragment of S2E12 monoclonal antibody, heavy chain, Fab fragment of S2E12 monoclonal antibody, light chain, GLYCEROL, ... (5 entities in total)
• Functional Keywords: sars-cov-2, neutralizing mab, antiviral protein, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 47751.24

Authors

Snell, G.,Czudnochowski, N.,Ng, C. (deposition date: 2020-09-12, release date: 2020-10-07, Last modification date: 2024-10-23)

Primary citation

Tortorici, M.A.,Beltramello, M.,Lempp, F.A.,Pinto, D.,Dang, H.V.,Rosen, L.E.,McCallum, M.,Bowen, J.,Minola, A.,Jaconi, S.,Zatta, F.,De Marco, A.,Guarino, B.,Bianchi, S.,Lauron, E.J.,Tucker, H.,Zhou, J.,Peter, A.,Havenar-Daughton, C.,Wojcechowskyj, J.A.,Case, J.B.,Chen, R.E.,Kaiser, H.,Montiel-Ruiz, M.,Meury, M.,Czudnochowski, N.,Spreafico, R.,Dillen, J.,Ng, C.,Sprugasci, N.,Culap, K.,Benigni, F.,Abdelnabi, R.,Foo, S.C.,Schmid, M.A.,Cameroni, E.,Riva, A.,Gabrieli, A.,Galli, M.,Pizzuto, M.S.,Neyts, J.,Diamond, M.S.,Virgin, H.W.,Snell, G.,Corti, D.,Fink, K.,Veesler, D.
Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms.
Science, 370:950-957, 2020

PubMed Abstract: Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.

PubMed: 32972994
DOI: 10.1126/science.abe3354

Experimental method

X-RAY DIFFRACTION (1.38 Å)