hcv replicon

PSI-6206 (RO 2433) 是 PSI-6130 的脱氨衍生物，PSI-6206 是一种选择性 HCV RNA 聚合酶抑制剂，低效抑制HCV 复制，EC90为 >100 μM。PSI-6130 是一种有效的选择性 HCV NS5B 聚合酶抑制剂。

Inarigivir soproxil (SB9200) 是一种先天免疫激动剂。 它还显示出针对耐药丙型肝炎病毒 (HCV) 变体的有效抗病毒活性。在基因型 1 HCV 复制子系统细胞中， HCV 1a 1b 的 EC50 为 2.2 和 1.0 μM。

2'-C-Methyladenosine 是丙型肝炎病毒(HCV)复制的抑制剂，分离自肾棒状杆菌。2'-C-Methyladenosine 抑制 HCV 复制子和 NS5B 催化的 RNA 合成，IC50值分别为 0.3 μM 和 1.9 μM。2'-C-Methyladenosine 还对Leishmania guyanensis (Lgy)和Leishmania braziliensis中的 LRV1有抑制作用。

MK-0608 是一种可口服的体外 HCV 复制抑制剂。在亚基因组复制子测定中，EC50值为 0.3 μM，EC90值为 1.3 μM。

R-1479 (4'-Azidocytidine) 是一种 RdRp 抑制剂，对于 HCV 亚基因组复制子系统中的 HCV RNA 复制，IC50 值为 1.28 μM。

Furaprofen 是一种可口服且具有选择性和高效性的 HCV 抑制剂，具有抗炎活性，抑制卡拉胶诱导的大鼠爪水肿，抑制较高剂量的大鼠棉粒诱导的肉芽肿。

Daclatasvir dihydrochloride (BMS-790052 dihydrochloride) 是有机阴离子转运多肽 1B(OATP1B) 和 OATP1B3抑制剂，IC50分别为 1.5 µM 和 3.27 µM。它也具有口服活性的 HCV NS5A 蛋白抑制剂，多种 HCV 复制子基因型的 EC50范围为 9-146 pM。

Velpatasvir (GS-5816) 是一种的 HCV NS5A 抑制剂。它也是 SARS-CoV 3CLpro 的抑制剂，IC50为 2.16 μM。

2'-O-Methylcytidine 是 2'-代核苷，可抑制 HCV 复制。 它在体外抑制 NS5B 催化的 RNA 合成，其抑制方式是与底物核苷三磷酸竞争。

RO8191 (CDM-3008) 是干扰素 (IFN) 受体激动剂。它直接与 IFNα β 受体 2 结合，激活 IFN 刺激的基因表达和 JAK STAT 磷酸化。它通过具有干扰素样活性发挥 cccDNA 调节剂作用，并具有抗 HBV 活性。

Boceprevir (SCH 503034) 是一种口服有效的选择性 HCV NS3 蛋白酶抑制剂。在酶试验中的 Ki 为 14 nM，在基于细胞的复制子试验中 EC90 为 350 nM。它也是 SARS-CoV-2 3CLpro 抑制剂。

Daclatasvir (EBP 883) 是一种高度选择性的 HCV NS5A 抑制剂，EC50 为 9-50 pM，适用于细胞培养中的多种 HCV 复制子基因型和 JFH-1 基因型 2a 感染性病毒。

ITMN4077 对感染人类 HuH7 细胞的丙型肝炎病毒具有抗病毒活性，评估为抑制 HCV 亚基因组复制子复制，EC50 为 2.131μM。

Sofosbuvir D6 is the deuterium labeled Sofosbuvir. Sofosbuvir is an active inhibitor of HCV RNA replication in the HCV replicon assay, demonstrates potent anti-hepatitis C virus (HCV) activity.

Sofosbuvir impurity B is the less active impurity of Sofosbuvir. Sofosbuvir is an active HCV RNA replication inhibitor in the HCV replicon assay, with potent anti-hepatitis C virus (HCV) activity.

Sofosbuvir impurity C is the less active impurity of Sofosbuvir. Sofosbuvir is an active HCV RNA replication inhibitor in the HCV replicon assay,with potent anti-hepatitis C virus (HCV) activity.

Sofosbuvir impurity D is the less active impurity of Sofosbuvir. Sofosbuvir is an active HCV RNA replication inhibitor in the HCV replicon assay,with potent anti-hepatitis C virus (HCV) activity.

Sofosbuvir impurity E is the less active impurity of Sofosbuvir. Sofosbuvir is an active HCV RNA replication inhibitor in the HCV replicon assay,with potent anti-hepatitis C virus (HCV) activity.

JTK-853 is a novel, non-nucleoside inhibitor of Hepatitis C Virus (HCV) polymerase. It also displays effective antiviral activity in HCV replicon cells (EC50s: 0.38 and 0.035 µM in genotype 1a H77 and 1b Con1 strains, respectively).

NHC-triphosphate triammonium is an active phosphorylated intracellular metabolite of β-d-N4-Hydroxycytidine (NHC) as a triphosphate form[1]. NHC-triphosphate triammonium is a weak alternative substrate for the viral polymerase and can be incorporated into HCV replicon RNA[1][2]. In an intracellular metabolism assay, HCV replicon cells are treated with 10 μM 3H-labeled NHC, and intracellular nucleotide levels are determined after 1, 2 and 8 hours incubations. NHC is rapidly convered into the mono-, di-, and triphosphate forms, and NHC-TP reaches up to 71.12 pM after 8 hours[1].NHC-triphosphate triammonium (NHC-TP) (5-40 μM) absence leads to full-length polymerization products, it can be a weak alternative substrate. In addition, incorporation of NHC-TP instead of CTP increases the molecular weight of the polymerization product by 16 (one extra oxygen) for each event and an obvious electrophoretic shift is observed in cell-free HCV NS5B polymerization reactions[1].Huh-7 cells are incubated with (10-50 μM; 4 h) NHC or a McGuigan phosphoramidate prodrug of NHC. Intracellular levels of the parental compounds and phosphorylated metabolites are measured using LC-MS MS. Small amounts of NHC-monophosphate (MP) and NHC-diphosphate (DP) can be observed, while NHC-triphosphate triammonium remains the most abundant metabolite[2].NHC-triphosphate triammonium (NHC-TP) metabolite may directly target the viral polymerase and behave as a nonobligate chain terminator. It plays a prominent role in inhibiting early negative-strand RNA synthesis, either through chain termination or mutagenesis, which may in turn interfere with correct replicase complex formation. [1]. Stuyver LJ,et al. Ribonucleoside analogue that blocks replication of bovine viral diarrhea and hepatitis C viruses in culture.Antimicrob Agents Chemother. 2003 Jan;47(1):244-54. [2]. Maryam Ehteshami, et al. Characterization of β-d- N4-Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus.

Dasabuvir (ABT-333) sodium 是非核苷丙型肝炎病毒 (HCV) 聚合酶抑制剂。Dasabuvir sodium 对 HCV NS5B 基因编码的 RNA 依赖性 RNA 聚合酶 (RNA polymerase) 表现出抑制作用。Dasabuvir sodium 能够抑制基因型 1a (菌株 H77) 复制子 (EC50: 7.7 nM) 和 1b (菌株 Con1) 复制子 (EC50: 1.8 nM)。

HCV-IN-39 (Compound 18a) 是一种有效的、口服具有活力的 hepatitis C virus (HCV) 核苷抑制剂，能够作用于 GT1a 复制子 (EC50: 0.259 μM)、GT1b 复制子 (EC50: 0.434 μM) 和 GT1b CES1 复制子 (EC50: 0.069 μM)。

Lomibuvir (VCH-222) 是丙型肝炎病毒 NS5B 聚合酶的一种非核苷变构抑制剂，Kd 值为 17 nM，已证明具有临床疗效。Lomibuvir 抑制 1b Con1 型 HCV 亚基因组复制子，EC50为 5.2 nM。Lomibuvir 优先抑制延长的 RNA 合成，而非从头合成的 RNA。

BMS-824 is a potent NS5A inhibitor. The 50% inhibition of HCV replicon replication for BMS-824 was approximately 5 nM, with a therapeutic index of >10,000. BMS-824 showed good specificity for HCV, as it was not active against several other RNA and DNA viruses.