7K9Z

Crystal structure of SARS-CoV-2 receptor binding domain in complex with the Fab fragments of neutralizing antibodies 298 and 52

Summary for 7K9Z

• Entry DOI: 10.2210/pdb7k9z/pdb
• Descriptor: 52 Fab Heavy Chain, 52 Fab Light Chain, 298 Fab Light Chain, ... (6 entities in total)
• Functional Keywords: sars-cov-2, receptor binding domain, neutralizing antibodies, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 120012.92

Authors

Newton, J.C.,Kucharska, I.,Rujas, E.,Cui, H.,Julien, J.P. (deposition date: 2020-09-29, release date: 2020-10-28, Last modification date: 2024-10-23)

Primary citation

Rujas, E.,Kucharska, I.,Tan, Y.Z.,Benlekbir, S.,Cui, H.,Zhao, T.,Wasney, G.A.,Budylowski, P.,Guvenc, F.,Newton, J.C.,Sicard, T.,Semesi, A.,Muthuraman, K.,Nouanesengsy, A.,Aschner, C.B.,Prieto, K.,Bueler, S.A.,Youssef, S.,Liao-Chan, S.,Glanville, J.,Christie-Holmes, N.,Mubareka, S.,Gray-Owen, S.D.,Rubinstein, J.L.,Treanor, B.,Julien, J.P.
Multivalency transforms SARS-CoV-2 antibodies into ultrapotent neutralizers.
Nat Commun, 12:3661-3661, 2021

PubMed Abstract: SARS-CoV-2, the virus responsible for COVID-19, has caused a global pandemic. Antibodies can be powerful biotherapeutics to fight viral infections. Here, we use the human apoferritin protomer as a modular subunit to drive oligomerization of antibody fragments and transform antibodies targeting SARS-CoV-2 into exceptionally potent neutralizers. Using this platform, half-maximal inhibitory concentration (IC) values as low as 9 × 10 M are achieved as a result of up to 10,000-fold potency enhancements compared to corresponding IgGs. Combination of three different antibody specificities and the fragment crystallizable (Fc) domain on a single multivalent molecule conferred the ability to overcome viral sequence variability together with outstanding potency and IgG-like bioavailability. The MULTi-specific, multi-Affinity antiBODY (Multabody or MB) platform thus uniquely leverages binding avidity together with multi-specificity to deliver ultrapotent and broad neutralizers against SARS-CoV-2. The modularity of the platform also makes it relevant for rapid evaluation against other infectious diseases of global health importance. Neutralizing antibodies are a promising therapeutic for SARS-CoV-2.

PubMed: 34135340
DOI: 10.1038/s41467-021-23825-2

Experimental method

X-RAY DIFFRACTION (2.95 Å)