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Review
. 2018 Dec 17;10(12):721.
doi: 10.3390/v10120721.

Development of Small-Molecule MERS-CoV Inhibitors

Ruiying Liang  1 , Lili Wang  2 , Naru Zhang  3 , Xiaoqian Deng  4 , Meng Su  5 , Yudan Su  6 , Lanfang Hu  7 , Chen He  8 , Tianlei Ying  9 , Shibo Jiang  10 , Fei Yu  11
Affiliations
Review

Development of Small-Molecule MERS-CoV Inhibitors

Ruiying Liang et al. Viruses. .

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) with potential to cause global pandemics remains a threat to the public health, security, and economy. In this review, we focus on advances in the research and development of small-molecule MERS-CoV inhibitors targeting different stages of the MERS-CoV life cycle, aiming to prevent or treat MERS-CoV infection.

Keywords: MERS-CoV; mechanism of action; small-molecule inhibitor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Summary of morbidity statistics with country- and quarter-level panel data.
Figure 2
Figure 2
Schematic diagram of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. MERS-CoV enters host cells by plasma membrane fusion (membrane fusion) or endosomal membrane fusion (endocytosis), and then releases the viral RNA into the cytoplasm. The RNA genome is replicated and viral proteins are produced. The progeny virus is generated and released from the infected cells.
Figure 3
Figure 3
Schematic representation of MERS-CoV S (spike) protein S1 subunit and S2 subunit. RBD, receptor binding domain; FP, fusion peptide; HR1, heptad repeat 1 domain; HR2, heptad repeat 2 domain; TM, transmembrane domain; CP, cytoplasmic domain. The residue numbers of each region correspond to their positions in the S protein of MERS-CoV. HR2P, the peptide derived from the HR2 domain of MERS-CoV S protein S2 subunit; HR2P-M2, HR2P analogous peptide with mutations.
Figure 4
Figure 4
Schematic representation of the inhibition mechanism of HR2P and HR2P-M2. ① Target cell membrane; ② MERS-CoV; ③ dipeptidyl peptidase-4 (DPP4). (A) Mechanism of normal binding between a host cell and MERS-CoV. MERS-CoV enters the host cell by binding the viral particle via the RBD in spike protein to the cellular receptorDPP4 on the surface of the host cell. The HR2 binds to the HR1 to form a six-helix bundle (6-HB) fusion core, which brings viral and cell membranes into close apposition for fusion. (B) HR2P and HR2P-M2 block six-bundle fusion core formation between HR1 and HR2 peptides by binding to the viral S protein HR1 domain.
Figure 5
Figure 5
Chemical structure formulae of small-molecule inhibitors of MERS-CoV described in this review.
Figure 5
Figure 5
Chemical structure formulae of small-molecule inhibitors of MERS-CoV described in this review.
Figure 5
Figure 5
Chemical structure formulae of small-molecule inhibitors of MERS-CoV described in this review.
Figure 5
Figure 5
Chemical structure formulae of small-molecule inhibitors of MERS-CoV described in this review.
Figure 5
Figure 5
Chemical structure formulae of small-molecule inhibitors of MERS-CoV described in this review.
Figure 5
Figure 5
Chemical structure formulae of small-molecule inhibitors of MERS-CoV described in this review.
Figure 5
Figure 5
Chemical structure formulae of small-molecule inhibitors of MERS-CoV described in this review.
Figure 5
Figure 5
Chemical structure formulae of small-molecule inhibitors of MERS-CoV described in this review.
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