Hung M, Patel P, Davis S, Green S R
RiboGene Inc., Hayward, California 94545, USA.
J Virol. 1998 Jun;72(6):4819-24. doi: 10.1128/JVI.72.6.4819-4824.1998.
The recent development and use of protease inhibitors have demonstrated the essential role that combination therapy will play in the treatment of individuals infected with the human immunodeficiency virus type 1 (HIV-1). Past clinical experience suggests that due to the appearance of resistant HIV-1 variants, additional therapeutics will be required in the future. To identify new options for combination therapy, it is of paramount importance to pursue novel targets for drug development. Ribosomal frameshifting is one potential target that has not been fully explored. Data presented here demonstrate that small molecules can stimulate frameshifting, leading to an imbalance in the ratio of Gag to Gag-Pol and inhibiting HIV-1 replication at what appears to be the point of viral particle assembly. Thus, we propose that frameshifting represents a new target for the identification of novel anti-HIV-1 therapeutics.
蛋白酶抑制剂的最新研发与应用已表明联合疗法在治疗人类免疫缺陷病毒1型（HIV-1）感染者方面将发挥的关键作用。过去的临床经验表明，由于耐药HIV-1变体的出现，未来将需要更多的治疗方法。为了确定联合疗法的新选择，寻求新的药物开发靶点至关重要。核糖体移码是一个尚未得到充分探索的潜在靶点。此处呈现的数据表明，小分子可以刺激移码，导致Gag与Gag-Pol比例失衡，并在似乎是病毒颗粒组装点的位置抑制HIV-1复制。因此，我们提出移码代表了鉴定新型抗HIV-1治疗药物的一个新靶点。
