De Novo Design of alpha-Helical Lipopeptides Targeting Viral Fusion Proteins: A Promising Strategy for Relatively Broad-Spectrum Antiviral Drug Discovery
机构：[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]Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, United States[5]Department of Clinical Trial Center, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China重点科室诊疗科室神经病学中心神经病学中心首都医科大学附属天坛医院
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 alpha-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 alpha-helical peptide plus a hydrocarbon tail. Promisingly, the constructs adopted stable alpha-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 alpha-helical coiled-coil domains present in all class I fusion proteins and the amphiphilic nature of the individual helices from this multihelix motif.
基金：
National Science Foundation of ChinaNational Natural Science Foundation of China [81573266, 81630090]; Beijing Nova ProgramBeijing Municipal Science & Technology Commission [Z181100006218115]; National Science and Technology Major Project of China [2018ZX09711003]; National Key Research and Development Program of China [2016YFC1201000, 2016YFC1200400]
第一作者机构：[1]State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Tai-Ping Road, Beijing 100850, China
共同第一作者：
通讯作者：
通讯机构：[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[4]Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, United States
推荐引用方式(GB/T 7714)：
Wang Chao,Zhao Lei,Xia Shuai,et al.De Novo Design of alpha-Helical Lipopeptides Targeting Viral Fusion Proteins: A Promising Strategy for Relatively Broad-Spectrum Antiviral Drug Discovery[J].JOURNAL OF MEDICINAL CHEMISTRY.2018,61(19):8734-8745.doi:10.1021/acs.jmedchem.8b00890.
APA：
Wang, Chao,Zhao, Lei,Xia, Shuai,Zhang, Tianhong,Cao, Ruiyuan...&Liu, Keliang.(2018).De Novo Design of alpha-Helical Lipopeptides Targeting Viral Fusion Proteins: A Promising Strategy for Relatively Broad-Spectrum Antiviral Drug Discovery.JOURNAL OF MEDICINAL CHEMISTRY,61,(19)
MLA：
Wang, Chao,et al."De Novo Design of alpha-Helical Lipopeptides Targeting Viral Fusion Proteins: A Promising Strategy for Relatively Broad-Spectrum Antiviral Drug Discovery".JOURNAL OF MEDICINAL CHEMISTRY 61..19(2018):8734-8745
医学