hcv in 4

HCV-IN-4, a potent and orally active inhibitor of HCV NS5A, demonstrates significant efficacy against genotypes GT1a, GT2b, GT3a, and the GT1a mutations Y93H and L31V. Its half-maximal effective concentrations (EC90s) are 3 pM, 0.3 nM, 0.01 nM, 0.5 nM, and 0.02 nM, respectively[1].

HCVNS4A Protein (18-40) (JT strain) 为HCVNS4A 肽，由第18至40个NS4A蛋白残基构成，能够增强NS3蛋白酶的催化效率。

HCV-IN-41 (compound 4) 是一种高效的丙肝病毒 (HCV)抑制剂，对 HCV1b、2a、3a 和 4a 的 EC50分别为 0.006762 nM、5.183 nM、1.365 nM 和 142.2 nM。HCV-IN-41 能降低 HCVRNA 的复制。

HCV-IN-46 (compound 6d)，一种抑制HCV的化合物，其EC50值为3.717 μM，展现出显著的抗病毒活性。

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)。

HCV-IN-43（化合物2）为HCVNS5B蛋白抑制剂，有效抑制丙型肝炎病毒（HCV）复制，适用于HCV感染研究。

HCV-IN-44（化合物28）为一种针对HCVNS5B蛋白的抑制剂，能够有效阻止丙型肝炎病毒（HCV）的复制。此化合物主要应用于HCV感染的相关研究。

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。

Beclabuvir (BMS-791325) 是一种高效的 NS5A 复制复合物抑制剂，抑制 HCV 基因型 1，2，4，5 表达的 NS5B 蛋白活性，可用于研究 HCV 感染。

6-Hydroxypyridin-3-ylboronic acid is a heterocyclic building block.1,2It has been used in the synthesis of non-nucleoside inhibitors of hepatitis C virus (HCV) RNA-dependent RNA polymerase nonstructural protein 5B (NS5B).16-Hydroxypyridin-3-ylboronic acid has also been used in the synthesis of mammalian target of rapamycin (mTOR) inhibitors.2 1.Hendricks, R.T., Spencer, S.R., Blake, J.F., et al.3-Hydroxyisoquinolines as inhibitors of HCV NS5b RNA-dependent RNA polymeraseBioorg. Med. Chem. Lett.19(2)410-414(2009) 2.Verheijen, J.C., Richard, D.J., Curran, K., et al.Discovery of 4-morpholino-6-aryl-1H-pyrazolo[3,4-d]pyrimidines as highly potent and sselective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR): Optimization of the 6-aryl substituentJ. Med. Chem.52(24)8010-8024(2009)

NHC-diphosphate is an active phosphorylated intracellular metabolite of β-d-N4-Hydroxycytidine (NHC) as a diphosphate form[1]. NHC is a pyrimidine ribonucleoside and behaves as a potent anti-virus agent. NHC effectively inhibits the replication of venezuelan equine encephalitis virus (VEEV), Chikungunya virus (CHIKV) and hepatitis C virus (HCV)[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 can be observed, while NHC-triphosphate remains the most abundant metabolite.[1].

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.

Ribavirin-13C5is intended for use as an internal standard for the quantification of ribavirin by GC- or LC-MS. Ribavirin is an antiviral guanosine nucleoside analog.1,2Upon entry into cells, ribavirin is metabolized to an active triphosphate form that induces viral RNA chain termination and inhibits viral polymerases. It reduces replication in a panel of seven RNA and four DNA viruses in Vero cells (EC50s = 2-95 μg/ml).3Ribavirin also reduces replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Vero cells (EC50= 109.5 μM).4Aerosol administration of ribavirin (30 mg/kg) reduces mortality in a mouse model of influenza A infection.5Formulations containing ribavirin have been used in the treatment of respiratory syncytial virus (RSV), hepatitis C virus (HCV), and viral hemorrhagic fevers. 1.Gilbert, B.E., and Knight, V.Biochemistry and clinical applications of ribavirinAntimicrob. Agents Chemother.30(2)201-205(1986) 2.Gordon, C.J., Tchesnokov, E.P., Woolner, E., et al.Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potencyJ. Biol. Chem.295(20)6785-6797(2020) 3.Kirsi, J.J., North, J.A., McKernan, P.A., et al.Broad-spectrum antiviral activity of 2-β-D-ribofuranosylselenazole-4-carboxamide, a new antiviral agentAntimicrob. Agents Chemother.24(3)353-361(1983) 4.Wang, M., Cao, R., Zhang, L., et al.Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitroCell Res.30(3)269-271(2020) 5.Wilson, S.Z., Knight, V., Wyde, P.R., et al.Amantadine and ribavirin aerosol treatment of influenza A and B infection in miceAntimicrob. Agents Chemother.17(4)642-648(1980)

Grazoprevir (MK-5172) 是一种氮杂大环化合物，被作为丙型肝炎病毒 NS3 4A 蛋白酶抑制剂。Grazoprevir 常与 elbasvir 联合用于治疗成人慢性 HCV 基因型 1 或 4 感染。

Beclabuvir, also known as BMS-791325, is an allosteric inhibitor that binds to thumb site 1 of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. BMS-791325 inhibits recombinant NS5B proteins from HCV genotypes 1, 3, 4, and 5 at 50% inhibitory concentrations (IC50) below 28 nM. In cell culture, BMS-791325 inhibited replication of HCV subgenomic replicons representing genotypes 1a and 1b at 50% effective concentrations (EC50s) of 3 nM and 6 nM, respectively, with similar (3 to 18 nM) values for genotypes 3a, 4a, and 5a. B

NS5A-IN-4 (Compound 1.12) 是一种具有口服活性的泛基因型丙型肝炎病毒 (HCV)NS5A 抑制剂，对gT1b、gT1a、gT2a、gT3a,gT4a 和gT5a 的IC50分别为 1.2、2296、4.6、362、10.3 和 693 pM。

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。