PT  - JOURNAL ARTICLE
AU  - Clara G. Altomare
AU  - Daniel C. Adelsberg
AU  - Juan Manuel Carreno
AU  - Iden A. Sapse
AU  - Fatima Amanat
AU  - Ali H. Ellebedy
AU  - Viviana Simon
AU  - Florian Krammer
AU  - Goran Bajic
TI  - Structure of a germline-like human antibody defines a neutralizing epitope on the SARS-CoV-2 spike NTD
AID  - 10.1101/2021.07.08.451649
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.07.08.451649
4099  - http://biorxiv.org/content/early/2021/07/08/2021.07.08.451649.short
4100  - http://biorxiv.org/content/early/2021/07/08/2021.07.08.451649.full
AB  - Structural characterization of infection- and vaccination-elicited antibodies in complex with antigen provides insight into the evolutionary arms race between the host and the pathogen and informs rational vaccine immunogen design. We isolated a germline-like monoclonal antibody (mAb) from plasmablasts activated upon mRNA vaccination against SARS-CoV-2 and determined its structure in complex with the spike glycoprotein by cryo-EM. We show that the mAb engages a previously uncharacterized neutralizing epitope on the spike N-terminal domain (NTD). The high-resolution structure reveals details of the intermolecular interactions and shows that the mAb inserts its HCDR3 loop into a hydrophobic NTD cavity previously shown to bind a heme metabolite, biliverdin. We demonstrate direct competition with biliverdin and that - because of the conserved nature of the epitope – the mAb maintains binding to viral variants B.1.1.7 and B.1.351. Our study illustrates the feasibility of targeting the NTD to achieve broad neutralization against SARS-CoV-2 variants.Competing Interest StatementThe authors have declared no competing interest.