PT - JOURNAL ARTICLE AU - Seth J. Zost AU - Pavlo Gilchuk AU - Rita E. Chen AU - James Brett Case AU - Joseph X. Reidy AU - Andrew Trivette AU - Rachel S. Nargi AU - Rachel E. Sutton AU - Naveenchandra Suryadevara AU - Elaine C. Chen AU - Elad Binshtein AU - Swathi Shrihari AU - Mario Ostrowski AU - Helen Y. Chu AU - Jonathan E. Didier AU - Keith W. MacRenaris AU - Taylor Jones AU - Samuel Day AU - Luke Myers AU - F. Eun-Hyung Lee AU - Doan C. Nguyen AU - Ignacio Sanz AU - David R. Martinez AU - Ralph S. Baric AU - Larissa B. Thackray AU - Michael S. Diamond AU - Robert H. Carnahan AU - James E. Crowe, Jr. TI - Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein AID - 10.1101/2020.05.12.091462 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.05.12.091462 4099 - http://biorxiv.org/content/early/2020/05/13/2020.05.12.091462.short 4100 - http://biorxiv.org/content/early/2020/05/13/2020.05.12.091462.full AB - Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date1,2. In response, we used a rapid antibody discovery platform to isolate hundreds of human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike (S) protein. We stratify these mAbs into five major classes based on their reactivity to subdomains of S protein as well as their cross-reactivity to SARS-CoV. Many of these mAbs inhibit infection of authentic SARS-CoV-2 virus, with most neutralizing mAbs recognizing the receptor-binding domain (RBD) of S. This work defines sites of vulnerability on SARS-CoV-2 S and demonstrates the speed and robustness of new antibody discovery methodologies.Competing Interest StatementR.S.B. has served as a consultant for Takeda and Sanofi Pasteur on issues related to vaccines. M.S.D. is a consultant for Inbios Vir Biotechnology, NGM Biopharmaceuticals, Eli Lilly, and on the Scientific Advisory Board of Moderna, and a recipient of unrelated research grants from Moderna and Emergent BioSolutions. J.E.C. has served as a consultant for Sanofi and is on the Scientific Advisory Boards of CompuVax and Meissa Vaccines, is a recipient of previous unrelated research grants from Moderna and Sanofi and is Founder of IDBiologics, Inc. Vanderbilt University has applied for patents concerning SARS-CoV-2 antibodies that are related to this work. F.E.-H.L., D.C.N., and I.S. are inventors on a patent submitted for the plasmablast survival medium. J.D. and K.W.M. are employees of Berkeley Lights, Inc. All other authors declared no competing interests.