Host-targeting agents in the treatment of hepatitis C: a beginning and an end?
Host-targeting agents in the treatment of hepatitis C: a beginning and an end?
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在治疗丙型肝炎的宿主靶向剂中：开始和结束？
DOI：
10.1016/j.antiviral.2013.09.020
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发表时间：
2013-11
影响因子：
7.6
通讯作者：
Gallay, Philippe A.
中科院分区：
文献类型：
--
作者：
Baugh, James M.;Garcia-Rivera, Jose A.;Gallay, Philippe A.
两种不同类型的丙型肝炎抗病毒药物，直接作用抗病毒药物（DAA）和宿主靶向抗病毒药物（HTAs）的开发，通过在感染患者中产生更高的持续病毒学应答（SVR）率，通过与旧标准治疗相比减少不良副作用和治疗持续时间，明显影响了丙型肝炎病毒（HCV）领域。今天，DAA被积极纳入标准治疗，并继续接受最先进的临床试验分析。随着大量创新和有效的第二代DAA化合物目前正在临床试验中进行测试，很明显，DAA的未来看起来非常光明。与其他类别的化合物相比，HTA的影响力略低，尽管HCV的主要治疗方案始于使用HTA -干扰素α（IFNα）。该化合物的优点在于它提供了广泛的抗病毒反应;然而，有害的副作用和病毒/患者抗性已经使该化合物过时。HTA研究已经向前发展，以HCV病毒进入和复制所需的许多细胞宿主因子为目标，如清道夫受体-BI（SR-BI），3-羟基-3-甲基戊二酰-CoA还原酶（HMGCoA还原酶），亲环素A（CypA），脂肪酸合成酶（Festival）和miRNA-122。追求这些HTAs背后的基本原理是基于真核细胞内发生的极低突变率，从而产生抗HCV化合物耐药性的高遗传屏障，以及对所有HCV基因型和血清型的泛基因型覆盖。随着丙型肝炎病毒（HCV）的终结，重要的是要询问是否还应结合其他DAA分析新型HTAs的发展，以解决潜在的难以治疗的HCV患者人群。既然HCV的治疗方案始于全球HTA的使用，那么是否也可以结束这一领域？
The development of two distinct classes of hepatitis C antiviral agents, direct-acting antivirals (DAAs) and host-targeting antivirals (HTAs), have distinctly impacted the hepatitis C virus (HCV) field by generating higher sustained virological response (SVR) rates within infected patients, via reductions in both adverse side effects and duration of treatment when compared to the old standard of care. Today DAAs are actively incorporated into the standard of care and continue to receive the most advanced clinical trial analysis. With a multitude of innovative and potent second-generation DAA compounds currently being tested in clinical trials, it is clear that the future of DAAs looks very bright. In comparison to the other class of compounds, HTAs have been slightly less impactful, despite the fact that primary treatment regimens for HCV began with the use of an HTA - interferon alpha (IFNα). The compound was advantageous in that it provided a broad-reaching antiviral response; however deleterious side effects and viral/patient resistance has since made the compound outdated. HTA research has since moved onward to target a number of cellular host factors that are required for HCV viral entry and replication such as scavenger receptor-BI (SR-BI), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoA reductase), cyclophilin A (CypA), fatty acid synthase (FASN) and miRNA-122. The rationale behind pursuing these HTAs is based upon the extremely low mutational rate that occurs within eukaryotic cells, thereby creating a high genetic barrier to drug resistance for anti-HCV compounds, as well as pan-genotypic coverage to all HCV genotypes and serotypes. As the end appears near for HCV, it becomes important to ask if the development of novel HTAs should also be analyzed in combination with other DAAs, in order to address potential hard-to-treat HCV patient populations. Since the treatment regimens for HCV began with the use of a global HTA, could one end the field as well?
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影响因子：
3.7
作者：
Coelmont L;Hanoulle X;Chatterji U;Berger C;Snoeck J;Bobardt M;Lim P;Vliegen I;Paeshuyse J;Vuagniaux G;Vandamme AM;Bartenschlager R;Gallay P;Lippens G;Neyts J
通讯作者：
Neyts J
影响因子：
13.5
作者：
Flisiak, Robert;Horban, Andrzej;Scalfaro, Pietro
通讯作者：
Scalfaro, Pietro
影响因子：
4.9
作者：
Friborg, Jacques;Levine, Steven;McPhee, Fiona
通讯作者：
McPhee, Fiona
DOI：
10.1073/pnas.0902693106
发表时间：
2009-05-05
影响因子：
11.1
作者：
Berger, Kristi L.;Cooper, Jacob D.;Randall, Glenn
通讯作者：
Randall, Glenn
影响因子：
100.3
作者：
Heim, Markus H.
通讯作者：
Heim, Markus H.