Humanized antibody potently neutralizes all SARS-CoV-2 variants by a novel mechanism

• DOI: 10.1101/2022.06.26.497634
• Publication Date: 2022-06-27T03:25:12Z
• Authors: Sai Luo; Jun Zhang; Alex J.B. Kreutzb...; Amanda Eaton; Robert J. Edwards; Changbin Jing; Hai-Qiang Dai; Gregory D. Sempowski; Kenneth Cronin; Robert Parks; Adam Yongxin Ye; Katayoun Mansouri; Maggie Barr; Novalia Pishesha; Aimee Chapdelaine...; Lucas Vieira Fran...; Anand Saminathan; Hanqin Peng; Himanshu Batra; Lorenza Bellusci; Surender Khurana; S. Munir Alam; David C. Montefiori; Kevin O. Saunders; Ming Tian; Hidde Ploegh; Tom Kirchhausen; Bing Chen; Barton F. Haynes; Frederick W. Alt
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

Abstract SARS-CoV-2 Omicron variants have generated a world-wide health crisis due to resistance most approved neutralizing antibodies and evasion of induced by vaccination. Here, we describe the SP1-77 antibody that was from humanized mouse model with single human V H 1-2 Vκ1-33-associated immensely diverse complementarity-determining-region-3 (CDR3) sequences. potently broadly neutralizes concern binds spike protein receptor-binding-domain (RBD) via novel-CDR3-based mode. does not block RBD-binding ACE2-receptor or endocytosis step viral entry, but rather blocks membrane fusion. Our findings provide first mechanistic insight into how non-ACE2 blocking SARS-CoV-2, which may inform strategies for designing vaccines robustly neutralize current future variants.