A non-competing pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2

Neutralizing antibodies could be antivirals against COVID-19 pandemics. Here, we report the isolation of four human-origin monoclonal antibodies from a convalescent patient in China. All of these isolated antibodies display neutralization abilities in vitro. Two of them (B38 and H4) block the binding between RBD and vial cellular receptor ACE2. Further competition assay indicates that B38 and H4 recognize different epitopes on the RBD, which is ideal for a virus-targeting mAb-pair to avoid immune escape in the future clinical applications. Moreover, therapeutic study on the mouse model validated that these two antibodies can reduce virus titers in the infected mouse lungs. Structure of RBD-B38 complex revealed that most residues on the epitope are overlapped with the RBD-ACE2 binding interface, which explained the blocking efficacy and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide the structural basis of rational vaccine design. One Sentence Summary A pair of human neutralizing monoclonal antibodies against COVID-19 compete cellular receptor binding but with different epitopes, and with post-exposure viral load reduction activity. ### Competing Interest Statement Y.W., F.W., C.S., D.L., S.T., Y.L, G.F.G and L.L. are listed as inventors on pending patent applications for mAb B38 and H4. The other authors declare that they have no competing interests. ### Funding Statement This work was supported by Zhejiang University special scientific research fund for COVID-19 prevention and control (2020XGZX019), the National Science and Technology Major Project (2018ZX10733403), the National Key R&D Program of China (2018YFC1200603), the National Key Plan for Scientific Research and Development of China (2016YFD0500304), National Natural Science Foundation of China (81902058), and the National Science and Technology Major Projects of Infectious Disease Funds (2017ZX10304402). ### Author Declarations All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All the data and reagents presented in this study are available from the corresponding authors upon request.