Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 11, Issue 22, Pages 19799-19807Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b04240
Keywords
gold nanorods; peptides; inhibitors; viral infections; MERS
Funding
- National Key Research and Development Program of China [2018YFB1105400]
- National Natural Science Foundation of China [21708019]
- Thousand Talents Program for Young Researchers
- Natural Science Foundation of Jiangsu Province [BK20180334]
- Shuangchuang Program of Jiangsu Province
- Fundamental Research Funds for Central Universities Nanjing University
- Scientific Research Foundation of Graduate School of Nanjing University [2017ZDL04]
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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 mu M, 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.
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