Tremblay Cécile L, Giguel Françoise, Kollmann Christopher, Guan Yongbiao, Chou Ting-Chao, Baroudy Bahige M, Hirsch Martin S
Massachusetts General Hospital, Infectious Diseases Unit, Harvard Medical School, Boston, Massachusetts 02114, USA.
Antimicrob Agents Chemother. 2002 May;46(5):1336-9. doi: 10.1128/AAC.46.5.1336-1339.2002.
SCH-C (SCH 351125) is a small-molecule antagonist of the human immunodeficiency virus type 1(HIV-1) coreceptor CCR5. It has in vitro activity against R5 viruses with 50% inhibitory concentrations ranging from 1.0 to 30.9 nM. We have studied anti-HIV-1 interactions of SCH-C with other antiretroviral agents in vitro. Synergistic interactions were seen with nucleoside reverse transcriptase inhibitors (zidovudine and lamivudine), nonnucleoside reverse transcriptase inhibitors (efavirenz), and protease inhibitors (indinavir) at all inhibitory concentrations evaluated. We have also studied antiviral interactions between the HIV-1 fusion inhibitor T-20 and SCH-C against a panel of R5 HIV-1 isolates. We found synergistic interactions against all the viruses tested, some of which harbored resistance mutations to reverse transcriptase and protease inhibitors. Anti-HIV-1 synergy was also observed between SCH-C and another R5 virus inhibitor, aminooxypentane-RANTES. These findings suggest that SCH-C may be a useful anti-HIV drug in combination regimens and that a combination of chemokine coreceptor/fusion inhibitors may be useful in the treatment of multidrug-resistant viruses.
SCH-C（SCH 351125）是1型人类免疫缺陷病毒（HIV-1）共受体CCR5的小分子拮抗剂。它对R5病毒具有体外活性，50%抑制浓度范围为1.0至30.9 nM。我们在体外研究了SCH-C与其他抗逆转录病毒药物的抗HIV-1相互作用。在所有评估的抑制浓度下，与核苷类逆转录酶抑制剂（齐多夫定和拉米夫定）、非核苷类逆转录酶抑制剂（依非韦伦）和蛋白酶抑制剂（茚地那韦）均观察到协同相互作用。我们还研究了HIV-1融合抑制剂T-20与SCH-C对一组R5 HIV-1分离株的抗病毒相互作用。我们发现对所有测试测试病毒均有协同相互作用，其中一些分离株对逆转录酶和蛋白酶抑制剂存在耐药突变。在SCH-C与另一种R5病毒抑制剂氨基氧基戊烷-RANTES之间也观察到抗HIV-1协同作用。这些发现表明，SCH-C在联合治疗方案中可能是一种有用的抗HIV药物，并且趋化因子共受体/融合抑制剂联合使用可能对治疗多重耐药病毒有用。
