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Review
. 2019 Jan 14;11(1):60.
doi: 10.3390/v11010060.

Advances in MERS-CoV Vaccines and Therapeutics Based on the Receptor-Binding Domain

Yusen Zhou  1   2 , Yang Yang  3 , Jingwei Huang  4 , Shibo Jiang  5 , Lanying Du  6
Affiliations
Review

Advances in MERS-CoV Vaccines and Therapeutics Based on the Receptor-Binding Domain

Yusen Zhou et al. Viruses. .

Abstract

Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is an infectious virus that was first reported in 2012. The MERS-CoV genome encodes four major structural proteins, among which the spike (S) protein has a key role in viral infection and pathogenesis. The receptor-binding domain (RBD) of the S protein contains a critical neutralizing domain and is an important target for development of MERS vaccines and therapeutics. In this review, we describe the relevant features of the MERS-CoV S-protein RBD, summarize recent advances in the development of MERS-CoV RBD-based vaccines and therapeutic antibodies, and illustrate potential challenges and strategies to further improve their efficacy.

Keywords: Coronavirus; MERS-CoV; receptor-binding domain; spike protein; therapeutics; vaccines.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Schematic structures of MERS-CoV S protein. (A) MERS-CoV genomic structure, with the untranslated region (UTR), open reading frame regions ORF1a and ORF1b, spike (S), envelope (E), membrane (M), and nucleocapsid (N) genes. (B) Schematic structure of the MERS-CoV virion and its major structural proteins. (C) Schematic structure of the MERS-CoV S protein and its functional domains, including the N-terminal domain (NTD), receptor-binding domain (RBD), receptor-binding motif (RBM), fusion peptide (FP), heptad repeat region 1 and 2 (HR1 and HR2), transmembrane region (TM), and cytoplasmic tail (CP). aa, amino acid; MERS-CoV, Middle East respiratory syndrome coronavirus; nt, nucleotide.
Figure 2
Figure 2
Structural basis of MERS-CoV S-protein RBD–DPP4 interaction. Structural data for the complex of MERS-CoV S-protein RBD bound to DPP4 are from the protein data bank (PDB) (ID: 4KR0). The MERS-CoV RBD core is colored in blue, the RBM is colored in red, and DPP4 is colored in green. The RBM residues directly involved in DPP4 binding are shown as sticks. DPP4, dipeptidyl peptidase 4; RBD, receptor-binding domain; RBM, receptor-binding motif; S, spike protein.
Figure 3
Figure 3
Models of the MERS-CoV S-protein trimer bound to DPP4. The models were generated by superimposing the MERS-CoV RBD in the structure of the MERS-CoV S-protein RBD–DPP4 complex (PDB ID: 4KR0) onto the RBDs in the structures of MERS-CoV S-protein trimers with (A) one RBD (PDB ID: 5X5F), (B) two RBDs (PDB ID: 5X5C), or (C) three RBDs (PDB ID: 5X59) in the “standing” conformation. The MERS-CoV S-protein trimers are colored in gray, with three RBDs colored in red, blue, and green. Three DPP4 dimers are colored in plum, orange, and yellow. DPP4, dipeptidyl peptidase 4; PDB, protein data bank; RBD, receptor-binding domain; S, spike protein.
Figure 4
Figure 4
Structural basis for MERS-CoV RBD recognition by neutralizing mAbs. (A) Crystal structure of MERS-CoV RBD complexed with MCA1 mAb (PDB ID: 5GMQ). (B) Crystal structure of the MERS-CoV RBD complexed with CDC2-C2 mAb (PDB ID: 6C6Z). (C) Crystal structure of the MERS-CoV RBD complexed with JC57-14 mAb (PDB ID: 6C6Y). (D) Crystal structure of MERS-CoV RBD complexed with MERS-4 mAb (PDB ID: 5ZXV). The MERS-CoV RBD core is colored in blue, the RBM is colored in red, and the heavy chains and light chains of each mAb are colored in green and yellow, respectively. The DPP4-binding residues that are blocked by each mAb are shown as sticks. mAb, monoclonal antibody; MERS-CoV, Middle East respiratory syndrome coronavirus; PDB, protein data bank; RBD, receptor-binding domain; RBM, receptor-binding motif.
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References

    1. Zaki A.M., van Boheemen S., Bestebroer T.M., Osterhaus A.D., Fouchier R.A. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 2012;367:1814–1820. doi: 10.1056/NEJMoa1211721. - DOI - PubMed
    1. Sha J., Li Y., Chen X., Hu Y., Ren Y., Geng X., Zhang Z., Liu S. Fatality risks for nosocomial outbreaks of Middle East respiratory syndrome coronavirus in the Middle East and South Korea. Arch. Virol. 2017;162:33–44. doi: 10.1007/s00705-016-3062-x. - DOI - PMC - PubMed
    1. Rivers C.M., Majumder M.S., Lofgren E.T. Risks of death and severe disease in patients with Middle East respiratory syndrome coronavirus, 2012-2015. Am. J. Epidemiol. 2016;184:460–464. doi: 10.1093/aje/kww013. - DOI - PMC - PubMed
    1. Yang Y.M., Hsu C.Y., Lai C.C., Yen M.F., Wikramaratna P.S., Chen H.H., Wang T.H. Impact of comorbidity on fatality rate of patients with Middle East respiratory syndrome. Sci. Rep. 2017;7:11307. doi: 10.1038/s41598-017-10402-1. - DOI - PMC - PubMed
    1. Matsuyama R., Nishiura H., Kutsuna S., Hayakawa K., Ohmagari N. Clinical determinants of the severity of Middle East respiratory syndrome (MERS): A systematic review and meta-analysis. BMC Public Health. 2016;16:1203. doi: 10.1186/s12889-016-3881-4. - DOI - PMC - PubMed

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