Potent MERS-CoV Fusion Inhibitory Peptides Identified from HR2 Domain in Spike Protein of Bat Coronavirus HKU4
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cells, Viruses and Peptides
2.2. Coronavirus Phylogenetic Analysis
2.3. Circular Dichroism Spectroscopic Analysis
2.4. Native Polyacrylamide Gel Electrophoresis (N-PAGE)
2.5. Cell–Cell Fusion Assay
2.6. Generation and Packaging of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Pseudovirus
2.7. Time-of-Addition Assay
2.8. Time-of-Removal Assay
2.9. Cytotoxicity Assay
3. Results
3.1. Design of HKU4 HR2-Peptides
3.2. Interaction between MERS-HR1P and HKU4 HR2-Derived Peptides
3.3. Inhibition of MERS-CoV S Protein-Mediated Cell–Cell Fusion
3.4. Inhibition of Pseudotyped MERS-CoVs Infection
4. Discussion
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Peptide | Average Hydro-Philicity | Solubility (μM) in | Inhibitory Activity of Peptides, IC50 (μM) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
PBS (pH 7.2) | Water | Cell–Cell Fusion | Pseudovirus Infection | ||||||||||
Q1020 | Q1020H | Q1020R | |||||||||||
Mean | SD | Mean | SD | Mean | SD | Mean | SD | Mean | SD | Mean | SD | ||
HKU4-HR2P1 | 0.0 | 1569 | 110 | 651 | 40 | 1.09 | 0.21 | 2.15 | 0.17 | 2.72 | 0.59 | 2.42 | 0.93 |
HKU4-HR2P2 | 0.2 | 2924 | 131 | 150 | 25 | 0.38 | 0.01 | 0.34 | 0.06 | 0.44 | 0.1 | 0.3 | 0.04 |
HKU4-HR2P3 | 0.0 | 118 | 13 | 1674 | 73 | 0.55 | 0.06 | 0.48 | 0.08 | 0.52 | 0.1 | 0.4 | 0.03 |
MERS-HR2P | −0.2 | 105 | 12 | 29 | 14 | 1.07 | 0.22 | 1.14 | 0.02 | 1.71 | 0.02 | 1.31 | 0.07 |
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Xia, S.; Lan, Q.; Pu, J.; Wang, C.; Liu, Z.; Xu, W.; Wang, Q.; Liu, H.; Jiang, S.; Lu, L. Potent MERS-CoV Fusion Inhibitory Peptides Identified from HR2 Domain in Spike Protein of Bat Coronavirus HKU4. Viruses 2019, 11, 56. https://doi.org/10.3390/v11010056
Xia S, Lan Q, Pu J, Wang C, Liu Z, Xu W, Wang Q, Liu H, Jiang S, Lu L. Potent MERS-CoV Fusion Inhibitory Peptides Identified from HR2 Domain in Spike Protein of Bat Coronavirus HKU4. Viruses. 2019; 11(1):56. https://doi.org/10.3390/v11010056
Chicago/Turabian StyleXia, Shuai, Qiaoshuai Lan, Jing Pu, Cong Wang, Zezhong Liu, Wei Xu, Qian Wang, Huan Liu, Shibo Jiang, and Lu Lu. 2019. "Potent MERS-CoV Fusion Inhibitory Peptides Identified from HR2 Domain in Spike Protein of Bat Coronavirus HKU4" Viruses 11, no. 1: 56. https://doi.org/10.3390/v11010056
APA StyleXia, S., Lan, Q., Pu, J., Wang, C., Liu, Z., Xu, W., Wang, Q., Liu, H., Jiang, S., & Lu, L. (2019). Potent MERS-CoV Fusion Inhibitory Peptides Identified from HR2 Domain in Spike Protein of Bat Coronavirus HKU4. Viruses, 11(1), 56. https://doi.org/10.3390/v11010056