Author: Wang, Nianshuang; Rosen, Osnat; Wang, Lingshu; Turner, Hannah L.; Stevens, Laura J.; Corbett, Kizzmekia S.; Bowman, Charles A.; Pallesen, Jesper; Shi, Wei; Zhang, Yi; Leung, Kwanyee; Kirchdoerfer, Robert N.; Becker, Michelle M.; Denison, Mark R.; Chappell, James D.; Ward, Andrew B.; Graham, Barney S.; McLellan, Jason S.
Title: Structural Definition of a Neutralization-sensitive Epitope on the MERS-CoV S1-NTD Cord-id: bd8b8xaa Document date: 2019_9_1
ID: bd8b8xaa
Snippet: 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 MERS-CoV S1 N-terminal domain (S1-NTD). Structu
Document: 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 MERS-CoV S1 N-terminal domain (S1-NTD). Structures of G2 alone and in complex with the MERS-CoV S1-NTD defined a site of vulnerability comprising two loops, each of which contained a residue mutated in G2-escape variants. Cell-surface binding studies and in vitro competition experiments demonstrated that G2 strongly disrupts the attachment of MERS-CoV S to its receptor DDP4, with the inhibition requiring the native trimeric S conformation. These results advance our understanding of antibody-mediated neutralization of coronaviruses and should facilitate development of immunotherapeutics and vaccines against MERS-CoV.
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