7MKM

SARS-CoV-2 Spike RBD in complex with neutralizing Fab SARS2-38 (local refinement)

Summary for 7MKM

• Entry DOI: 10.2210/pdb7mkm/pdb
• EMDB information: 23898 23899
• Descriptor: Spike protein S1, SARS2-38 Fv heavy chain, SARS2-38 Fv light chain, ... (4 entities in total)
• Functional Keywords: glycoprotein, antibody, viral protein-immune system complex, structural genomics, center for structural genomics of infectious diseases, csgid, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 3
• Total formula weight: 45379.63

Authors

Adams, L.J.,Fremont, D.H.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2021-04-24, release date: 2021-05-12, Last modification date: 2024-10-23)

Primary citation

VanBlargan, L.A.,Adams, L.J.,Liu, Z.,Chen, R.E.,Gilchuk, P.,Raju, S.,Smith, B.K.,Zhao, H.,Case, J.B.,Winkler, E.S.,Whitener, B.M.,Droit, L.,Aziati, I.D.,Bricker, T.L.,Joshi, A.,Shi, P.Y.,Creanga, A.,Pegu, A.,Handley, S.A.,Wang, D.,Boon, A.C.M.,Crowe Jr., J.E.,Whelan, S.P.J.,Fremont, D.H.,Diamond, M.S.
A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope.
Immunity, 54:2399-2416.e6, 2021

PubMed Abstract: With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here, we developed a panel of neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) that bound the receptor binding domain of the spike protein at distinct epitopes and blocked virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Although several potently neutralizing mAbs protected K18-hACE2 transgenic mice against infection caused by ancestral SARS-CoV-2 strains, others induced escape variants in vivo or lost neutralizing activity against emerging strains. One mAb, SARS2-38, potently neutralized all tested SARS-CoV-2 variants of concern and protected mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engaged a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of neutralizing antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants.

PubMed: 34481543
DOI: 10.1016/j.immuni.2021.08.016

Experimental method

ELECTRON MICROSCOPY (3.16 Å)