Structural Definition of a Neutralization-Sensitive Epitope on the MERS-CoV S1-NTD

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2019 Sep 26

PMID 31553909

Citations 47

Authors

Nianshuang Wang

Osnat Rosen

Lingshu Wang

Hannah L Turner

Laura J Stevens

Kizzmekia S Corbett

Charles A Bowman

Jesper Pallesen

Wei Shi

Yi Zhang

Kwanyee Leung

Robert N Kirchdoerfer

Michelle M Becker

Mark R Denison

James D Chappell

Andrew B Ward

Barney S Graham

Jason S McLellan

Affiliations

Soon will be listed here.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human population in 2012 and has caused substantial morbidity and mortality. Potently neutralizing antibodies targeting the receptor-binding domain (RBD) on MERS-CoV spike (S) protein have been characterized, but much less is known about antibodies targeting non-RBD epitopes. Here, we report the structural and functional characterization of G2, a neutralizing antibody targeting the MERS-CoV S1 N-terminal domain (S1-NTD). Structures of G2 alone and in complex with the MERS-CoV S1-NTD define a site of vulnerability comprising two loops, each of which contain a residue mutated in G2-escape variants. Cell-surface binding studies and in vitro competition experiments demonstrate that G2 strongly disrupts the attachment of MERS-CoV S to its receptor, dipeptidyl peptidase-4 (DPP4), with the inhibition requiring the native trimeric S conformation. These results advance our understanding of antibody-mediated neutralization of coronaviruses and should facilitate the development of immunotherapeutics and vaccines against MERS-CoV.

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