Daming ZhouHelen M.E. DuyvesteynCheng Pin ChenChung Guei HuangTing Hua ChenShin Ru ShihYi Chun LinChien Yu ChengShu Hsing ChengYhu Chering HuangTzou Yien LinChe MaJiandong HuoLoic CarriqueTomas MalinauskasReinis R. RuzaPranav N.M. ShahTiong Kit TanPramila RijalRobert F. DonatKerry GodwinKaren R. ButtigiegJulia A. TreeJulika RadeckeNeil G. PatersonPiyada SupasaJuthathip MongkolsapayaGavin R. ScreatonMiles W. CarrollJavier Gilbert-JaramilloMichael L. KnightWilliam JamesRaymond J. OwensJames H. NaismithAlain R. TownsendElizabeth E. FryYuguang ZhaoJingshan RenDavid I. StuartKuan Ying A. HuangPublic Health EnglandDiamond Light SourceAcademia Sinica, Genomics Research CenterNational Yang-Ming University TaiwanChang Gung Memorial HospitalUniversity of OxfordTaipei Medical UniversityChang Gung UniversitySir William Dunn School of PathologyFaculty of Medicine, Siriraj Hospital, Mahidol UniversityNuffield Department of MedicineMRC Weatherall Institute of Molecular MedicineThe Rosalind Franklin InstituteResearch Complex2020-08-252020-08-252020-01-01Nature Structural and Molecular Biology. (2020)15459985154599932-s2.0-85088842557https://repository.li.mahidol.ac.th/handle/20.500.14594/57771© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. The COVID-19 pandemic has had an unprecedented health and economic impact and there are currently no approved therapies. We have isolated an antibody, EY6A, from an individual convalescing from COVID-19 and have shown that it neutralizes SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds the receptor binding domain (RBD) of the viral spike glycoprotein tightly (KD of 2 nM), and a 2.6-Å-resolution crystal structure of an RBD–EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues within this footprint are key to stabilizing the pre-fusion spike. Cryo-EM analyses of the pre-fusion spike incubated with EY6A Fab reveal a complex of the intact spike trimer with three Fabs bound and two further multimeric forms comprising the destabilized spike attached to Fab. EY6A binds what is probably a major neutralizing epitope, making it a candidate therapeutic for COVID-19.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1038/s41594-020-0480-y