7U9P

SARS-CoV-2 spike trimer RBD in complex with Fab NA8

Summary for 7U9P

• Entry DOI: 10.2210/pdb7u9p/pdb
• EMDB information: 26404
• Descriptor: Spike glycoprotein, NA8 Fab heavy chain, NA8 Fab light chain, ... (4 entities in total)
• Functional Keywords: sars-cov-2, covid19, spike protein, antibody, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 4
• Total formula weight: 330626.19

Authors

Tsybovsky, Y.,Kwong, P.D.,Farci, P. (deposition date: 2022-03-11, release date: 2022-11-23)

Primary citation

Chen, Z.,Zhang, P.,Matsuoka, Y.,Tsybovsky, Y.,West, K.,Santos, C.,Boyd, L.F.,Nguyen, H.,Pomerenke, A.,Stephens, T.,Olia, A.S.,Zhang, B.,De Giorgi, V.,Holbrook, M.R.,Gross, R.,Postnikova, E.,Garza, N.L.,Johnson, R.F.,Margulies, D.H.,Kwong, P.D.,Alter, H.J.,Buchholz, U.J.,Lusso, P.,Farci, P.
Potent monoclonal antibodies neutralize Omicron sublineages and other SARS-CoV-2 variants.
Cell Rep, 41:111528-111528, 2022

PubMed Abstract: The emergence and global spread of the SARS-CoV-2 Omicron variants, which carry an unprecedented number of mutations, raise serious concerns due to the reduced efficacy of current vaccines and resistance to therapeutic antibodies. Here, we report the generation and characterization of two potent human monoclonal antibodies, NA8 and NE12, against the receptor-binding domain of the SARS-CoV-2 spike protein. NA8 interacts with a highly conserved region and has a breadth of neutralization with picomolar potency against the Beta variant and the Omicron BA.1 and BA.2 sublineages and nanomolar potency against BA.2.12.1 and BA.4. Combination of NA8 and NE12 retains potent neutralizing activity against the major SARS-CoV-2 variants of concern. Cryo-EM analysis provides the structural basis for the broad and complementary neutralizing activity of these two antibodies. We confirm the in vivo protective and therapeutic efficacies of NA8 and NE12 in the hamster model. These results show that broad and potent human antibodies can overcome the continuous immune escape of evolving SARS-CoV-2 variants.

PubMed: 36302375
DOI: 10.1016/j.celrep.2022.111528

Experimental method

ELECTRON MICROSCOPY (3.5 Å)