1区 · 生物学
Article
作者: Richter, Anja ; Bertzbach, Luca D ; Dietert, Kristina ; Hoffmann, Julius ; Endres, Matthias ; Wilson, Ian A ; Homeyer, Marie A ; Jeworowski, Lara Maria ; Schwarz, Tatjana ; Gruber, Achim D ; Skriner, Karl ; van Hoof, Scott ; Suttorp, Norbert ; Sander, Leif E ; Corman, Victor Max ; Liu, Hejun ; Stöffler, Laura ; Yuan, Meng ; Barthel, Paula Charlotte ; Kurth, Florian ; Hocke, Andreas C ; Li, Lucie Y ; Schmitz, Dietmar ; von Wardenburg, Niels ; Schmidt, Marie Luisa ; Abdelgawad, Azza ; Wu, Nicholas C ; Trimpert, Jakob ; Reincke, S Momsen ; Vladimirova, Daria ; Witzenrath, Martin ; Prüss, Harald ; Osterrieder, Nikolaus ; Kreye, Jakob ; Müller, Marcel Alexander ; Drosten, Christian ; Hippenstiel, Stefan ; Höltje, Markus ; Zhu, Xueyong ; Sánchez-Sendin, Elisa ; Kornau, Hans-Christian ; Wendisch, Daniel ; Franke, Christiana ; Lee, Chang-Chun D
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 IC50 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.
