Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein | Zendy

Senyan Zhang | Zendy; Pan-Pan Zhou | Zendy; Pengfei Wang | Zendy; Yangyang Li | Zendy; Liwei Jiang | Zendy; Wenxu Jia | Zendy; Han Wang | Zendy; Angela Fan | Zendy; Dongli Wang | Zendy; Xuanling Shi | Zendy; Xianyang Fang | Zendy; Michal Hammel | Zendy; Shuying Wang | Zendy; Xinquan Wang | Zendy; Linqi Zhang | Zendy

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Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein

Author(s) -

Senyan Zhang,

Pan-Pan Zhou,

Pengfei Wang,

Yangyang Li,

Liwei Jiang,

Wenxu Jia,

Han Wang,

Angela Fan,

Dongli Wang,

Xuanling Shi,

Xianyang Fang,

Michal Hammel,

Shuying Wang,

Xinquan Wang,

Linqi Zhang

Publication year - 2018

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2018.06.041

Subject(s) - epitope , middle east respiratory syndrome coronavirus , neutralization , glycoprotein , mutagenesis , binding site , viral entry , plasma protein binding , antibody , microbiology and biotechnology , chemistry , receptor , biology , virology , computational biology , mutation , virus , genetics , covid-19 , viral replication , medicine , disease , pathology , gene , infectious disease (medical specialty)

The major mechanism of antibody-mediated neutralization of the Middle East respiratory syndrome coronavirus (MERS-CoV) involves competition with the cellular receptor dipeptidyl peptidase 4 (DPP4) for binding to the receptor-binding domain (RBD) of the spike (S) glycoprotein. Here, we report a unique epitope and unusual neutralizing mechanism of the isolated human antibody MERS-4. Structurally, MERS-4 approached the RBD from the outside of the RBD-DPP4 binding interface. Such binding resulted in the folding of the β5-β6 loop toward a shallow groove on the RBD interface critical for accommodating DPP4. The key residues for binding are identified through site-directed mutagenesis. Structural modeling revealed that MERS-4 binds to RBD only in the "up" position in the S trimer. Furthermore, MERS-4 demonstrated synergy with several reported antibodies. These results indicate that MERS-4 neutralizes MERS-CoV by indirect rather than direct competition with DPP4. This mechanism provides a valuable addition for the combined use of antibodies against MERS-CoV infection.

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