RT Journal Article
SR Electronic
T1 A glycan cluster on the SARS-CoV-2 spike ectodomain is recognized by Fab-dimerized glycan-reactive antibodies
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.30.178897
DO 10.1101/2020.06.30.178897
A1 Priyamvada Acharya
A1 Wilton Williams
A1 Rory Henderson
A1 Katarzyna Janowska
A1 Kartik Manne
A1 Robert Parks
A1 Margaret Deyton
A1 Jordan Sprenz
A1 Victoria Stalls
A1 Megan Kopp
A1 Katayoun Mansouri
A1 Robert J Edwards
A1 R. Ryan Meyerhoff
A1 Thomas Oguin
A1 Gregory Sempowski
A1 Kevin Saunders
A1 Barton F. Haynes
YR 2020
UL http://biorxiv.org/content/early/2020/06/30/2020.06.30.178897.abstract
AB The COVID-19 pandemic caused by SARS-CoV-2 has escalated into a global crisis. The spike (S) protein that mediates cell entry and membrane fusion is the current focus of vaccine and therapeutic antibody development efforts. The S protein, like many other viral fusion proteins such as HIV-1 envelope (Env) and influenza hemagglutinin, is glycosylated with both complex and high mannose glycans. Here we demonstrate binding to the SARS-CoV-2 S protein by a category of Fab-dimerized glycan-reactive (FDG) HIV-1-induced broadly neutralizing antibodies (bnAbs). A 3.1 Å resolution cryo-EM structure of the S protein ectodomain bound to glycan-dependent HIV-1 bnAb 2G12 revealed a quaternary glycan epitope on the spike S2 domain involving multiple protomers. These data reveal a new epitope on the SARS-CoV-2 spike that can be targeted for vaccine design.HighlightsFab-dimerized, glycan-reactive (FDG) HIV-1 bnAbs cross-react with SARS-CoV-2 spike.3.1 Å resolution cryo-EM structure reveals quaternary S2 epitope for HIV-1 bnAb 2G12.2G12 targets glycans, at positions 709, 717 and 801, in the SARS-CoV-2 spike.Our studies suggest a common epitope for FDG antibodies centered around glycan 709.Competing Interest StatementThe authors have declared no competing interest.