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 是有效的抗 HIV-1 杀微生物剂候选物格里菲辛 (GRFT) 的衍生物。我们使用对这种凝集素的敏感性降低的病毒 CAP206.08 和 CAAN5342.A2 将这些化合物的抗 HIV-1 活性与 GRFT 进行了比较。2MG 和 2MG3 串联体对无细胞和细胞相关病毒具有与 GRFT 相似的活性，而 3MG 和 4MG 明显更有效。此外，这些病毒中 234N 或 295N 聚糖的恢复，已知会增加对 GRFT 的敏感性，也增加了对 2MG 和 2MG3 的敏感性，而不是对 3MG 和 4MG 的敏感性。此外，体外产生的 GRFT 抗性病毒对 2MG 和 2MG3 的抵抗力相同，而对 3MG 和 4MG 的抵抗力相当低。最后，所有五种化合物在精液和阴道模拟物中都显示出增加的抑制活性，尽管在前者中效果更明显。这些数据支持将串联体作为潜在杀微生物剂的进一步研究。