Chappell JD

References (1)

Title : Structural Definition of a Neutralization-Sensitive Epitope on the MERS-CoV S1-NTD - Wang_2019_Cell.Rep_28_3395
Author(s) : Wang N , Rosen O , Wang L , Turner HL , Stevens LJ , Corbett KS , Bowman CA , Pallesen J , Shi W , Zhang Y , Leung K , Kirchdoerfer RN , Becker MM , Denison MR , Chappell JD , Ward AB , Graham BS , McLellan JS
Ref : Cell Rep , 28 :3395 , 2019
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.
ESTHER : Wang_2019_Cell.Rep_28_3395
PubMedSearch : Wang_2019_Cell.Rep_28_3395
PubMedID: 31553909