Baugh Simon D P
Fox Chase Chemical Diversity Center, Inc., 3805 Old Easton Rd, Doylestown PA 18902. United States.
Infect Disord Drug Targets. 2017;17(1):24-35. doi: 10.2174/1871526517666170104113730.
Chronic hepatitis B is a major global health issue, and has no known cure. Currently there are over 240 million people infected with the disease, and it leads to the death of over 686,000 people each year. A total of seven treatments which help to control the disease are currently available: interferon-based treatments (pegasys, and interferon alpha), and nucleoside and nucleotide analogs (Viread, Baraclude, Tyzeka, Hepsera, Epivir-HBV), but all require continuing treatment to maintain control of the disease. One of the definitions of a cure for hepatitis B virus (HBV) is the loss of hepatitis B surface antigen (HBsAg), the lipid envelope which surrounds the hepatitis B virus. The current interferon-based treatments, and nucleoside and nucleotide analogs give at most an approximately 10% rate of clearance of HBsAg. Other viral diseases such as HIV and hepatitis C have been most effectively treated with a combination of agents, and it is believed that the best opportunity for finding a cure for HBV will reside in a combination of therapies targeting different phases of the HBV lifecycle.A range of agents (small-molecules, natural products, macrocycles, and non-small molecules) have been described as having the ability to suppress the secretion of HBsAg (in vitro, as well as in vivo in animal models, pre-clinical models, and clinical trials), and this review will focus on an overview of the different agents, and different strategies being pursued to develop methods of inhibiting the secretion of HBsAg, with a view to the cure of HBV.
慢性乙型肝炎是一个重大的全球健康问题，目前尚无治愈方法。目前有超过2.4亿人感染该疾病，每年导致超过68.6万人死亡。目前共有七种有助于控制该疾病的治疗方法：基于干扰素的治疗方法（派罗欣和干扰素α）以及核苷和核苷酸类似物（韦瑞德、博路定、替比夫定、贺普丁、拉米夫定），但所有这些治疗都需要持续治疗以维持对疾病的控制。治愈乙型肝炎病毒（HBV）的定义之一是乙肝表面抗原（HBsAg）消失，乙肝表面抗原是包裹乙肝病毒的脂质包膜。目前基于干扰素的治疗方法以及核苷和核苷酸类似物清除HBsAg的比率最高约为10%。其他病毒疾病，如艾滋病和丙型肝炎，通过联合使用药物得到了最有效的治疗，人们认为找到治愈HBV的最佳机会在于针对HBV生命周期不同阶段的联合治疗。一系列药物（小分子、天然产物、大环化合物和非小分子）已被描述为具有抑制HBsAg分泌的能力（在体外以及动物模型、临床前模型和临床试验的体内实验中），本综述将重点概述不同的药物以及为开发抑制HBsAg分泌方法而采用的不同策略，以期治愈HBV。
