The authors thank Cindy Castado and Normand Blais (GSK Vaccines) for their help in the selection of the genetically divergent sarbecoviruses used in this study and Hideki Tani (University of Toyama) for providing the reagents necessary for preparing VSV pseudotyped viruses. Funding: This study was supported by the National Institute of Allergy and Infectious Diseases (DP1AI158186 and HHSN272201700059C to D.V.), National Institute of General Medical Sciences (5T32GM008268 to S.K.Z.), a Pew Biomedical Scholars Award (D.V.), an Investigators in the Pathogenesis of Infectious Disease Awards from the Burroughs Wellcome Fund (D.V.), Fast Grants (D.V.), the University of Washington Arnold and Mabel Beckman cryoEM center and the National Institute of Health grant S10OD032290 (to D.V.). J.D.B. and D.V. are investigators of the Howard Hughes Medical Institute. Author contributions: Y.J.P., A.D.M., T.N.S., Z.L., D.P., J.D.B., D.C., M.S.P. and D.V. designed the experiments; A.D.M., D.P., A.C.W., S.K.Z., K.S.S. F.Z., M.G., J.N. and F.A.L. isolated mAb and performed binding, neutralization assays and biolayer interferometry measurements; A.D.M. and D.P. performed ACE2 binding inhibition and S1 shedding assays; B.G. evaluated effector functions; T.N.S. and J.D.B. performed deep-mutational scanning; Z.L. and S.P.J.W. performed mutant selection and fitness assays; R.A., S.-Y.C.F., F.B., and J.N., D.C. and M.S.P. performed hamster model experiments and data analysis; Y.J.P. carried out cryoEM specimen preparation, data collection and processing. Y.J.P. and D.V. built and refined the atomic models. S.K.Z., A.J. and J.E.B. purified recombinant glycoproteins. Y.J.P., A.D.M., T.N.S., Z.L., D.P., J.D.B., D.C., M.S.P. and D.V. analyzed the data; Y.J.P., A.D.M., D.C., M.S.P. and D.V. wrote the manuscript with input from all authors; F.A.L., F.B., G.S., J.N., S.P.J.W., H.W.V., J.D.B., D.C., M.S.P. and D.V. supervised the project. Competing interests: A.D.M., D.P., F.Z., M.G., B.G., J.N., F.A.L., F.B., G.S., H.W.V., D.C., M.S.P. are employees of Vir Biotechnology Inc. and may hold shares in Vir Biotechnology Inc. D.C. is currently listed as an inventor on multiple patent applications, which disclose the subject matter described in this manuscript. J.D.B. is an inventor on patents licensed by Fred Hutchinson cancer research center related to deep mutational scanning of viral proteins. The Veesler and Neyts laboratories have received sponsored research agreements from Vir Biotechnology Inc. H.W.V. is a founder of PierianDx and Casma Therapeutics. Neither company provided funding for this work or is performing related work. J.D.B. consults for Moderna, Oncorus and Flagship Labs 77. Data and materials availability: The cryoEM map and coordinates have been deposited to the Electron Microscopy Databank and Protein Data Bank with the following accession numbers; SARS-CoV-2 S/S2K146 (3RBDs open) EMD-25785; SARS-CoV-2 S/S2K146 (2RBDs open) PDB 7TAT, EMD-25784; SARS-CoV-2 S RBD/S2K146 (Local refinement) PDB 7TAS, EMD-25783. Materials generated in this study will be made available on request, but we may require a completed materials transfer agreement signed with Vir Biotechnology or the University of Washington. This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material.