Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
Department of Analytical Biochemistry, Meiji Pharmaceutical University, Kiyose, Japan.
Semin Liver Dis. 2019 Feb;39(1):78-85. doi: 10.1055/s-0038-1676804. Epub 2019 Jan 17.
Identification of sodium taurocholate cotransporting polypeptide (NTCP) as an entry receptor for hepatitis B and D viruses (HBV and HDV) has not only promoted our understanding of the mechanism underlying the viral entry process, but also provided cell culture models supporting viral infection. These models have greatly facilitated cell-based chemical screening for the discovery of entry inhibitors, and mode of action studies using such inhibitors have shown the advantages of NTCP as a drug target. Furthermore, in vitro chemical screening by application of high-throughput affinity-based technologies that target NTCP has identified a variety of unique small molecules that interfere with viral entry. This review summarizes this hot topic in the development of HBV/HDV entry inhibitors, with special focus on the use of NTCP as a drug target.
鉴定牛磺胆酸钠共转运多肽（NTCP）作为乙型肝炎和丁型肝炎病毒（HBV 和 HDV）的进入受体，不仅促进了我们对病毒进入过程的机制的理解，还提供了支持病毒感染的细胞培养模型。这些模型极大地促进了基于细胞的化学筛选，以发现进入抑制剂，并且使用这些抑制剂的作用模式研究表明 NTCP 作为药物靶标的优势。此外，通过应用针对 NTCP 的高通量基于亲和力的技术进行体外化学筛选，已经鉴定出多种干扰病毒进入的独特小分子。本综述总结了乙型肝炎/丁型肝炎病毒进入抑制剂开发这一热门话题，特别关注 NTCP 作为药物靶标的应用。
