7SN1

Structure of human SARS-CoV-2 neutralizing antibody C1C-A3 Fab

Summary for 7SN1

• Entry DOI: 10.2210/pdb7sn1/pdb
• Descriptor: neutralizing antibody C1C-A3 Fab heavy chain, neutralizing antibody C1C-A3 Fab light chain (3 entities in total)
• Functional Keywords: covid-19, sars-cov-2, neutralizing antibody, neutralization escape, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 52918.71

Authors

Pan, J.,Abraham, J.,Clark, S. (deposition date: 2021-10-27, release date: 2021-12-08, Last modification date: 2024-10-30)

Primary citation

Nabel, K.G.,Clark, S.A.,Shankar, S.,Pan, J.,Clark, L.E.,Yang, P.,Coscia, A.,McKay, L.G.A.,Varnum, H.H.,Brusic, V.,Tolan, N.V.,Zhou, G.,Desjardins, M.,Turbett, S.E.,Kanjilal, S.,Sherman, A.C.,Dighe, A.,LaRocque, R.C.,Ryan, E.T.,Tylek, C.,Cohen-Solal, J.F.,Darcy, A.T.,Tavella, D.,Clabbers, A.,Fan, Y.,Griffiths, A.,Correia, I.R.,Seagal, J.,Baden, L.R.,Charles, R.C.,Abraham, J.
Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain.
Science, 375:eabl6251-eabl6251, 2022

PubMed Abstract: Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we evaluate the consequences of further viral evolution. We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans.

PubMed: 34855508
DOI: 10.1126/science.abl6251

Experimental method

X-RAY DIFFRACTION (1.467 Å)