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A Sars-Cov-2 Neutralizing Antibody Protects from Lung Pathology in a Covid-19 Hamster Model (preprint)
ssrn; 2020.
Preprint
in English
| PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3680870
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 IC 50 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.
Full text:
Available
Collection:
Preprints
Database:
PREPRINT-SSRN
Main subject:
COVID-19
/
Multiple Organ Failure
Language:
English
Year:
2020
Document Type:
Preprint
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