Abstract |
Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe acute respiratory syndrome-like illness with high pathogenicity and mortality due to the lack of effective therapeutics. Currently, only few antiviral agents are available for the treatment of MERS, but their effects have been greatly impaired by low antiviral activity, poor metabolic stability, and serious adverse effects. Therefore, the development of effective treatment for MERS is urgently needed. In this study, a series of heptad repeat 1 (HR1) peptide inhibitors have been developed to inhibit HR1/HR2-mediated membrane fusion between MERS-CoV and host cells, which is the major pathway of MERS-CoV-induced host infections. Particularly, peptide pregnancy-induced hypertension (PIH) exhibits potent inhibitory activity with IC50 of 1.171 μM, and its inhibitory effects can be further increased to 10-fold by forming a gold nanorod complex (PIH-AuNRs). In addition, PIH-AuNRs display enhanced metabolic stability and biocompatibility in vitro and in vivo and, therefore, effectively prevent MERS-CoV-associated membrane fusion. In summary, PIH-AuNRs represent a novel class of antiviral agents and have a great potential in treating MERS in the clinic.
|
Authors | Xinyu Huang, Meng Li, Yurui Xu, Jikang Zhang, Xia Meng, Xueying An, Lei Sun, Leilei Guo, Xue Shan, Junliang Ge, Jiao Chen, Yadong Luo, Heming Wu, Yu Zhang, Qing Jiang, Xinghai Ning |
Journal | ACS applied materials & interfaces
(ACS Appl Mater Interfaces)
Vol. 11
Issue 22
Pg. 19799-19807
(Jun 05 2019)
ISSN: 1944-8252 [Electronic] United States |
PMID | 31099550
(Publication Type: Journal Article)
|
Chemical References |
- Antiviral Agents
- Peptides
- Gold
|
Topics |
- Animals
- Antiviral Agents
(chemistry, pharmacology)
- Cell Line
- Circular Dichroism
- Female
- Gold
(chemistry)
- Humans
- Mice
- Middle East Respiratory Syndrome Coronavirus
(drug effects, pathogenicity)
- Nanotubes
(chemistry)
- Peptides
(chemistry, pharmacology)
- Protein Structure, Secondary
|