Council for Scientific and Industrial Research, Emerging Research Area Platform, Next Generation Health Cluster, Pretoria, Gauteng, South Africa.
Council for Scientific and Industrial Research, Emerging Research Area Platform, Next Generation Health Cluster, Pretoria, Gauteng, South Africa; University of the Witwatersrand, School of Pathology, Johannesburg, South Africa.
Virology. 2020 May;544:12-20. doi: 10.1016/j.virol.2020.01.017. Epub 2020 Feb 5.
Tandemers 2MG, 2MG3, 3MG and 4MG are derivatives of the potent anti-HIV-1 microbicide candidate griffithsin (GRFT). We compared these compounds anti-HIV-1 activity to GRFT using the viruses CAP206.08 and CAAN5342.A2 that have decreased sensitivity to this lectin. The 2MG and 2MG3 tandemers had similar activity to GRFT against cell-free and cell-associated viruses, while 3MG and 4MG were significantly more potent. Furthermore, the restoration of the 234N or 295N glycan in these viruses, known to increase sensitivity to GRFT, also increased sensitivity to 2MG and 2MG3, and not to 3MG and 4MG. In addition, GRFT resistant viruses generated in-vitro were equally resistant to 2MG and 2MG3 while they had considerably low resistance to 3MG and 4MG. Lastly, all five compounds showed increased inhibitory activity in seminal and vaginal simulants although the effect was more pronounced in the former. These data support further studies of tandemers as potential microbicides.
Tandemers 2MG、2MG3、3MG 和 4MG 是具有强大抗 HIV-1 功效的候选杀菌剂 griffithsin（GRFT）的衍生物。我们比较了这些化合物对具有降低对该凝集素敏感性的病毒 CAP206.08 和 CAAN5342.A2 的抗 HIV-1 活性与 GRFT。2MG 和 2MG3 串联物对游离病毒和细胞相关病毒的活性与 GRFT 相似，而 3MG 和 4MG 则明显更有效。此外，已知可增加对 GRFT 敏感性的 234N 或 295N 聚糖在这些病毒中的恢复也增加了对 2MG 和 2MG3 的敏感性，而对 3MG 和 4MG 则没有。此外，在体外产生的对 GRFT 具有抗性的病毒对 2MG 和 2MG3 同样具有抗性，而对 3MG 和 4MG 的抗性则相当低。最后，所有五种化合物在精液和阴道模拟物中均显示出增强的抑制活性，尽管在前者中的效果更为明显。这些数据支持进一步研究串联物作为潜在的杀菌剂。
