6XKP

Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibody CV07-270

Summary for 6XKP

• Entry DOI: 10.2210/pdb6xkp/pdb
• Related: 6XKQ
• Descriptor: Spike protein S1, CV07-270 Heavy Chain, CV07-270 Light Chain, ... (5 entities in total)
• Functional Keywords: sars-cov-2, antibody, spike, coronavirus, covid-19, immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 6
• Total formula weight: 148461.15

Authors

Liu, H.,Yuan, M.,Zhu, X.,Wu, N.C.,Wilson, I.A. (deposition date: 2020-06-26, release date: 2020-10-14, Last modification date: 2024-10-09)

Primary citation

Kreye, J.,Reincke, S.M.,Kornau, H.C.,Sanchez-Sendin, E.,Corman, V.M.,Liu, H.,Yuan, M.,Wu, N.C.,Zhu, X.,Lee, C.D.,Trimpert, J.,Holtje, M.,Dietert, K.,Stoffler, L.,von Wardenburg, N.,van Hoof, S.,Homeyer, M.A.,Hoffmann, J.,Abdelgawad, A.,Gruber, A.D.,Bertzbach, L.D.,Vladimirova, D.,Li, L.Y.,Barthel, P.C.,Skriner, K.,Hocke, A.C.,Hippenstiel, S.,Witzenrath, M.,Suttorp, N.,Kurth, F.,Franke, C.,Endres, M.,Schmitz, D.,Jeworowski, L.M.,Richter, A.,Schmidt, M.L.,Schwarz, T.,Muller, M.A.,Drosten, C.,Wendisch, D.,Sander, L.E.,Osterrieder, N.,Wilson, I.A.,Pruss, H.
A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model.
Cell, 183:1058-, 2020

PubMed Abstract: The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from 10 COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb, CV07-209, neutralized authentic SARS-CoV-2 with an IC value of 3.1 ng/mL. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 Å revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2-neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss, and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy.

PubMed: 33058755
DOI: 10.1016/j.cell.2020.09.049

Experimental method

X-RAY DIFFRACTION (2.72 Å)