A therapeutic non-self-reactive SARS-CoV-2 antibody protects from lung pathology in a COVID-19 hamster model. Kreye et al

Published: 16 September 2020| Version 1 | DOI: 10.17632/f6tb3csgjt.1
Jakob Kreye, S. Momsen Reincke, Hans-Christian Kornau, Elisa Sánchez-Sendin, Kristina Dietert, Ian A. Wilson, Harald Prüss


Supplementary information for "A therapeutic non-self-reactive SARS-CoV-2 antibody protects from lung pathology in a COVID-19 hamster model", Kreye, Reincke, Kornau et al. 2020. 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 ten COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb CV07-209 neutralized authentic SARS-CoV-2 with IC50 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. Table S1. Description of patient cohort. Table S2. Immunoglobulin sequence and functional screening data of all isolated mAbs. Table S3. Biophysical and functional characterization of the 18 most potent SARS-CoV-2 neutralizing mAbs. Table S4. X-ray data collection and refinement statistics. Table S5. Hydrogen bonds and salt bridges identified at the antibody-RBD interface using the PISA program. Table S6. Histopathological scoring of lung tissue from COVID-19 hamster model.



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