nCoV: Developing CoV-bnMABs for therapy of highly pathogenic coronaviruses including SARS-CoV-2

This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. Recently we have investigated antibody cross-reactivity between SARS-CoV and MERSCoV using a cohort (n=128) of SARS convalescent samples (serum and PBMC) collected during the 2003 outbreak in China. We isolated: • A panel of human mAbs (hmAbs) (n=12) specific to the cross-reactive epitopes between SARS-CoV and MERS-CoV by yeast-surface-display technology from PBMCs of SARS patients (Fig.1A) • Four of 12 hmAbs showing stronger neutralizing activities against both SARS- and MERS-CoVs in pseudotype (Fig.1B) or wild-type virus assays (Fig.1C), namely the CoV broadly neutralizing mAbs (CoV-bnMABs). Because a new highly pathogenic coronavirus (2019-nCoV renamed as SARS-CoV-2 by WHO on 11th Feb) outbreak occurred in December 2019 in China, we compared CoV sequences and alignments and found that the S protein (the major target of antibody response) of 2019-nCoV shares higher homology with SARS-CoV (77 %) as compared with MERS-CoV (35%). Thus, we hypothesize that some of CoV-bnMABs generated from SARS patients will cross react with SARS-CoV-2 in addition to MERS-CoV and SARSCoV. Indeed, our preliminary data (obtained on 9th Feb 2020) have shown that the CoVbnMABs can specifically bind to SARS-CoV-2 S protein expressed on the surface of 293T cells (Fig.2). Therefore, we propose here to further characterize the CoV-bnMABs in terms of protective efficacy against SARS-CoV-2 while scaling up antibody production for IND-enabling CoVbnMAB CMC development, aiming to rapidly develop therapeutic antibodies for the current outbreak. Technically, in collaboration with a team of experts from UK and China, we will accomplish essential pre-clinical studies within 12 months and prepare for clinical trials.