2. Academic Validation
  3. De Novo Design of α-Helical Lipopeptides Targeting Viral Fusion Proteins: A Promising Strategy for Relatively Broad-Spectrum Antiviral Drug Discovery

De Novo Design of α-Helical Lipopeptides Targeting Viral Fusion Proteins: A Promising Strategy for Relatively Broad-Spectrum Antiviral Drug Discovery

  • J Med Chem. 2018 Oct 11;61(19):8734-8745. doi: 10.1021/acs.jmedchem.8b00890.
Chao Wang 1,  Lei Zhao 1,  Shuai Xia 2,  Tianhong Zhang 1,  Ruiyuan Cao 1,  Guodong Liang 1,  Yue Li 3,  Guangpeng Meng 3,  Weicong Wang 4,  Weiguo Shi 1,  Wu Zhong 1,  Shibo Jiang 2 5,  Keliang Liu 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Toxicology and Medical Countermeasures , Beijing Institute of Pharmacology and Toxicology , 27 Tai-Ping Road , Beijing 100850 , China.
  • 2 Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences & Shanghai Public Health Clinical Center , Fudan University , 130 Dong An Road , Shanghai 200032 , China.
  • 3 Key Laboratory of Structure-Based Drug Design & Discovery of the Ministry of Education , Shenyang Pharmaceutical University , Shenyang 110016 , China.
  • 4 Department of Clinical Trial Center, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital , Capital Medical University , Beijing 100050 , China.
  • 5 Lindsley F. Kimball Research Institute , New York Blood Center , New York , New York 10065 , United States.
PMID: 30192544 DOI: 10.1021/acs.jmedchem.8b00890
Abstract

Class I enveloped viruses share similarities in their apparent use of a hexameric coiled-coil assembly to drive the merging of virus and host cell membranes. Inhibition of coiled coil-mediated interactions using bioactive Peptides that replicate an α-helical chain from the viral fusion machinery has significant Antiviral potential. Here, we present the construction of a series of lipopeptides composed of a de novo heptad repeat sequence-based α-helical peptide plus a hydrocarbon tail. Promisingly, the constructs adopted stable α-helical conformations and exhibited relatively broad-spectrum Antiviral activities against Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza A viruses (IAVs). Together, these findings reveal a new strategy for relatively broad-spectrum Antiviral drug discovery by relying on the tunability of the α-helical coiled-coil domains present in all class I fusion proteins and the amphiphilic nature of the individual helices from this multihelix motif.

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