Ivashchenko A V, Iamanushkin P M, Mit'kin O D, Ezhova E V, Korzinov O M, Bulanova E A, Koriakova A G, Vyshemirskaia P V, Bychko V V, Ivashchenko A A
Eksp Klin Farmakol. 2014;77(10):38-43.
Several novel compounds were found to be potent inhibitors of the HCV (JFH-1 isolate) infection in vitro. Human serum did not significantly reduce antiviral activity of the lead compound, AVR560 (< 4-fold). The immunohistochemistry studies with the Huh7 cell line, infectable with the HCV (JFH-1 strain), demonstrated that AVR560 inhibited the early steps of viral infection and blocked the spread of the HCV infection in tissue culture. The cytotoxicity in Huh7 and Vero-76 cell lines was mild. AVR560 proved to be a specific HCV inhibitor and exhibited no activity against other flaviviruses such as yellow fever (strain 17D), West Nile (strain NY99), and dengue (New Guinea type 2) in in vitro infection experiments. AVR560 also did not inhibit any of the tested human CYP450 isozymes (3A4, 1A2, 2C19 and 2D6). In the pharmacokinetic studies in mice, rats and dogs, favorable pharmacokinetic profiles and good oral bioavailability were observed for AV560. Further pre-clinical studies with this novel HCV inhibitor are in progress.
发现几种新型化合物在体外是丙型肝炎病毒（JFH-1分离株）感染的有效抑制剂。人血清不会显著降低先导化合物AVR560的抗病毒活性（降低幅度小于4倍）。对可被丙型肝炎病毒（JFH-1株）感染的Huh7细胞系进行的免疫组织化学研究表明，AVR560抑制病毒感染的早期步骤，并阻断丙型肝炎病毒感染在组织培养中的传播。在Huh7和Vero-76细胞系中的细胞毒性较轻。在体外感染实验中，AVR560被证明是一种特异性的丙型肝炎病毒抑制剂，对其他黄病毒如黄热病（17D株）、西尼罗河病毒（NY99株）和登革热病毒（新几内亚2型）没有活性。AVR560也不抑制任何测试的人细胞色素P450同工酶（3A4、1A2、2C19和2D6）。在小鼠、大鼠和犬的药代动力学研究中，观察到AV560具有良好的药代动力学特征和口服生物利用度。目前正在对这种新型丙型肝炎病毒抑制剂进行进一步的临床前研究。
