AUTHOR=Zhang Shuyuan , Jia Wenxv , Zeng Jianwei , Li Mingxi , Wang Ziyi , Zhou Haixia , Zhang Linqi , Wang Xinquan 

TITLE=Cryoelectron microscopy structures of a human neutralizing antibody bound to MERS-CoV spike glycoprotein

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.988298

DOI=10.3389/fmicb.2022.988298

ISSN=1664-302X

ABSTRACT=Neutralizing monoclonal antibodies (mAbs) to highly pathogenic coronaviruses represent promising candidates for clinical intervention. Here, we isolated a highly potent neutralizing monoclonal antibody MERS-S41 from the yeast displayed scFv library using the S protein as the bait. To uncover the neutralization mechanism, we determined the structures of MERS-S41 Fab in complex with the trimeric spike glycoprotein by cryoelectron microscopy (cryo-EM). We observed distinct classes of the complex structures, which showed that MERS-S41 Fab bound to the ‘up’ receptor binding domain (RBD) with full saturation and partially bound to accessible ‘down’ RBD, providing a structural basis for further understanding of mAbs bound to trimeric spike glycoproteins. Structure analysis of the epitope and cell surface staining assay demonstrated that the virus entry is blocked mainly via a direct competition with the host receptor dipeptidyl peptidase-4 (DPP4).