INHIBITION OF HIV REPLICATION BY NYSTATIN A AND OTHER AGENTS

制霉菌素 A 和其他药物抑制 HIV 复制

• 批准号: 3792580
• 负责人: M P SELVAM
• 金额: --
• 依托单位: CENTER BIOLOGICS EVALUATION RESEARCH TRANSFUSION
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3792580
• 关键词: HIV infections; RNA directed DNA polymerase; amphotericin B; foscarnet; human immunodeficiency virus 1; immunofluorescence technique; liposomes; monoclonal antibody; nystatin; polymerase chain reaction; tissue /cell culture; virus antigen; virus replication; western blottings

Nystatin A was compared with Amphotericin B and Foscarnet for their respective abilities to inhibit the replication of HIV-1 in H9 cells. Nystatin A and Amphotericin B are polyene macrolide antibiotics. Foscarnet is a trisodium phosphonoformate inhibitor of reverse transcriptase (RT). HIV-1 infected cells were cultured for seven days in the presence of 5-50 ug/ml concentrations of these three drugs, and RT activity and p24 antigen production were quantitated. Untreated HIV-1 infected H9 cells served as controls. Nystatin A was most effective inhibiting viral replication at 10 ug/ml, a concentration that did not affect cell viability. Nystatin A treatment inhibited RT activity by 95% and p24 production by 90% which was comparable to the level of inhibition mediated by Amphotericin B and Foscarnet. Western blot analysis of the HIV-infected H9 cells treated with these drugs did not detect any virus at the cellular level. These findings were further corroborated by indirect immunofluorescense studies using monoclonal anti-gp120 antibodies and FITC-conjugated secondary antibodies, and by polymerase chain reaction analysis using a 32P-labelled probe. These results suggest that Nystatin A merits attention as an antiviral drug for the treatment of HIV-1 infection. In vivo drug delivery by liposome encapsulation is currently under study.

制霉菌素A与两性霉素B和膦甲酸进行了比较， 抑制H9细胞中HIV-1复制的能力。 制霉菌素A和两性霉素B是多烯大环内酯类抗生素。 膦甲酸三钠是一种逆转录酶抑制剂， 转录酶（RT）。将HIV-1感染的细胞培养7天， 这三种药物的浓度为5 - 50 μ g/ml，RT 对活性和p24抗原产生进行定量。 未经治疗的HIV-1 感染的H9细胞作为对照。 制霉菌素A最有效 在10 μ g/ml浓度下抑制病毒复制， 影响细胞活力。 制霉菌素A处理抑制RT活性， 95%，p24产量增加90%，与 两性霉素B和膦甲酸介导的抑制作用。Western blot 对用这些药物处理的HIV感染的H9细胞的分析没有 在细胞水平上检测任何病毒。 这些发现进一步 通过使用单克隆抗体的间接免疫荧光研究证实 抗gp120抗体和FITC缀合的第二抗体，以及 使用32P标记的探针进行聚合酶链反应分析。 这些 结果提示制霉菌素A作为一种抗病毒药物值得关注 用于治疗HIV-1感染。 脂质体体内给药 目前正在研究封装。