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Review
. 2016 Sep:133:165-77.
doi: 10.1016/j.antiviral.2016.07.015. Epub 2016 Jul 26.

MERS-CoV spike protein: Targets for vaccines and therapeutics

Qihui Wang  1 , Gary Wong  2 , Guangwen Lu  3 , Jinghua Yan  4 , George F Gao  5
Affiliations
Review

MERS-CoV spike protein: Targets for vaccines and therapeutics

Qihui Wang et al. Antiviral Res. 2016 Sep.

Abstract

The disease outbreak caused by Middle East respiratory syndrome coronavirus (MERS-CoV) is still ongoing in the Middle East. Over 1700 people have been infected since it was first reported in September 2012. Despite great efforts, licensed vaccines or therapeutics against MERS-CoV remain unavailable. The MERS-CoV spike (S) protein is an important viral antigen known to mediate host-receptor binding and virus entry, as well as induce robust humoral and cell-mediated responses in humans during infection. In this review, we highlight the importance of the S protein in the MERS-CoV life cycle, summarize recent advances in the development of vaccines and therapeutics based on the S protein, and discuss strategies that can be explored to develop new medical countermeasures against MERS-CoV.

Keywords: Animal models; Coronavirus; MERS-CoV; Spike protein; Therapeutics; Vaccines.

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Figures

Fig. 1
Fig. 1
Timeline for the discovery of different human CoVs.
Fig. 2
Fig. 2
Genome arrangement of MERS-CoV and structure of the spike protein-receptor complex. (A) Schematic representation of the MERS-CoV genome. Abbreviations: nsp, nonstructural protein; 3CLpro, 3C-like protease; RdRp, RNA-dependent RNA polymerase; HEL1, superfamily 1 helicase; ExoN, 5′-3′ exonuclease; OMT, S-adenosylmethionine-dependent ribose 2′-O-methyltransferase; S, spike protein; orf, open reading frame; E, envelope protein; M, membrane protein; and N, nucleocapsid. In addition, PLpro (papain-like protease) is located in nsp3, and NendoU (nidoviral endoribonuclease specific for U) is located in nsp15. The gene coding for accessory protein orf8b overlaps with the N-coding gene (Cotten et al., 2013). (B) Schematic representation of the MERS-CoV spike protein. Abbreviations: SP, signal peptide; NTD, N-terminal domain; RBD, receptor binding domain; HR1/2, heptad repeat 1/2; and TM, transmembrane domain. (C) Complex structure between the MERS-RBD and its receptor CD26. The core and external subdomains are highlighted in cyan and magenta, respectively, while the receptor is colored in green for the β-propeller domain and in gray for the α/β-hydrolase domain, respectively. (D) Crystal structure of the HR1/HR2 fusion core. The three HR1/HR2 chains are colored in green, cyan, and magenta, respectively. The approximate size of the bundle is indicated. The left panel represents the top view, and the right panel represents the side view. The figure was used upon approval of the authors in Gao et al., 2013. (E) and (G) Ribbon diagrams showing the overall structures of MHV-S and HKU1-S trimers, respectively. (F) and (H) Ribbon diagrams showing one MHV-S and HKU1-S molecule, respectively. NTD, CTD and S2 are colored in blue, cyan, and magenta, respectively in E-H.
Fig. 3
Fig. 3
Comparison of the MERS-RBD binding sites among different antibodies. Top panels (A–D) show the superimposition of the structures between the indicated antibody (shown in ribbons) and the MERS-RBD (surface shown in cyan) with a previously reported structure of hCD26 (shown in green ribbons) bound to the MERS-RBD (Lu et al., 2013a). Antibodies D12 (Wang et al, 2015), 4C2 (Li et al., 2015), MERS27 (Yu et al. 2015), and m336 (Ying et al., 2015) are marked in yellow, magenta, blue, and orange, respectively. Bottom panels (E–H) indicate footprint overlaps in the MERS-RBD (surface shown in cyan) between the indicated antibody and hCD26. Residues recognized by the indicated antibody and hCD26 are represented in the same manner as the top panels. The overlapped interface residues are highlighted in red, and the amino acid identities/positions are labeled.
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