7KLG

SARS-CoV-2 RBD in complex with Fab 15033

Summary for 7KLG

• Entry DOI: 10.2210/pdb7klg/pdb
• Descriptor: Fab 15033 heavy chain, Fab 15033 light chain, Spike glycoprotein, ... (4 entities in total)
• Functional Keywords: sars-cov-2, spike glycoprotein, fab, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 139627.82

Authors

Li, Z.,Rini, J.M. (deposition date: 2020-10-30, release date: 2021-02-10, Last modification date: 2023-10-18)

Primary citation

Miersch, S.,Li, Z.,Saberianfar, R.,Ustav, M.,Brett Case, J.,Blazer, L.,Chen, C.,Ye, W.,Pavlenco, A.,Gorelik, M.,Garcia Perez, J.,Subramania, S.,Singh, S.,Ploder, L.,Ganaie, S.,Chen, R.E.,Leung, D.W.,Pandolfi, P.P.,Novelli, G.,Matusali, G.,Colavita, F.,Capobianchi, M.R.,Jain, S.,Gupta, J.B.,Amarasinghe, G.K.,Diamond, M.S.,Rini, J.,Sidhu, S.S.
Tetravalent SARS-CoV-2 Neutralizing Antibodies Show Enhanced Potency and Resistance to Escape Mutations.
J.Mol.Biol., 433:167177-167177, 2021

PubMed Abstract: Neutralizing antibodies (nAbs) hold promise as therapeutics against COVID-19. Here, we describe protein engineering and modular design principles that have led to the development of synthetic bivalent and tetravalent nAbs against SARS-CoV-2. The best nAb targets the host receptor binding site of the viral S-protein and tetravalent versions block entry with a potency exceeding bivalent nAbs by an order of magnitude. Structural studies show that both the bivalent and tetravalent nAbs can make multivalent interactions with a single S-protein trimer, consistent with the avidity and potency of these molecules. Significantly, we show that the tetravalent nAbs show increased tolerance to potential virus escape mutants and an emerging variant of concern. Bivalent and tetravalent nAbs can be produced at large-scale and are as stable and specific as approved antibody drugs. Our results provide a general framework for enhancing antiviral therapies against COVID-19 and related viral threats, and our strategy can be applied to virtually any antibody drug.

PubMed: 34329642
DOI: 10.1016/j.jmb.2021.167177

Experimental method

X-RAY DIFFRACTION (3.2 Å)