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Open AccessArticle

Peptide-Based Membrane Fusion Inhibitors Targeting HCoV-229E Spike Protein HR1 and HR2 Domains

by 1,†, 1,†, 1, 1, 1, 2, 1 and 1,2,3,*
Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China
Key Laboratory of Reproduction Regulation of National Population and Family Planning Commission, The Shanghai Institute of Planned Parenthood Research, Institute of Reproduction and Development, Fudan University, Shanghai 200032, China
Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(2), 487;
Received: 5 January 2018 / Revised: 24 January 2018 / Accepted: 31 January 2018 / Published: 6 February 2018
(This article belongs to the Special Issue Membrane Fusion)
Human coronavirus 229E (HCoV-229E) infection in infants, elderly people, and immunocompromised patients can cause severe disease, thus calling for the development of effective and safe therapeutics to treat it. Here we reported the design, synthesis and characterization of two peptide-based membrane fusion inhibitors targeting HCoV-229E spike protein heptad repeat 1 (HR1) and heptad repeat 2 (HR2) domains, 229E-HR1P and 229E-HR2P, respectively. We found that 229E-HR1P and 229E-HR2P could interact to form a stable six-helix bundle and inhibit HCoV-229E spike protein-mediated cell-cell fusion with IC50 of 5.7 and 0.3 µM, respectively. 229E-HR2P effectively inhibited pseudotyped and live HCoV-229E infection with IC50 of 0.5 and 1.7 µM, respectively. In a mouse model, 229E-HR2P administered intranasally could widely distribute in the upper and lower respiratory tracts and maintain its fusion-inhibitory activity. Therefore, 229E-HR2P is a promising candidate for further development as an antiviral agent for the treatment and prevention of HCoV-229E infection. View Full-Text
Keywords: HCoV-229E; membrane fusion; cell-cell fusion; peptide; inhibitor HCoV-229E; membrane fusion; cell-cell fusion; peptide; inhibitor
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MDPI and ACS Style

Xia, S.; Xu, W.; Wang, Q.; Wang, C.; Hua, C.; Li, W.; Lu, L.; Jiang, S. Peptide-Based Membrane Fusion Inhibitors Targeting HCoV-229E Spike Protein HR1 and HR2 Domains. Int. J. Mol. Sci. 2018, 19, 487.

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