The ability of antiviral polyamides (AVP) to act upon polyomaviruses (PyV) was evaluated. Initial studies found that a single treatment of AVP protected SV40-infected BSC-1 cells from cytopathic effect (CPE) for as long as 11 days p.i.. AVP substantially suppressed SV40 genome copy numbers over the duration of the experiment. Immunofluorescence analysis of ataxia-telangiectasia mutated (ATM) activation and large T antigen (LTag) expression clearly demonstrated that AVP treatment at day 1 p.i. delayed the onset of productive SV40 replication by approximately 3 days, and substantially limited the infection relative to vehicle-treated controls. AVP dose-response experiments recorded IC50s in the low nM range that were similar to IC50s previously reported for HPV16. The ability of AVPs to act on BKPyV was next examined. Again, IC50s in the low nM range were obtained with the exception of an AVP (PA1) that gave an IC50 of 437 nM against the BKPyV Dunlop strain. The Mre11 inhibitor Mirin substantially reduced the AVP IC50 against SV40 demonstrating that Mre11 protects PyV genomes from AVP action as previously shown for HPV. Together these experiments show that AVPs are potent antiviral agents for PyV that act via a mechanism with similarities to that found for HPV. The results demonstrate that AVPs are useful tools for controlling and studying PyV biology. The potential use of these agents against BKPyV and other PyV pathogens also has clinical implications.

评估了抗病毒聚酰胺（AVP）对多瘤病毒（PyV）起作用的能力。最初的研究发现，一次AVP处理可以保护SV40感染的BSC-1细胞，使其在感染后长达11天不受细胞病变作用（CPE）的影响。在实验过程中，AVP基本上抑制了SV40基因组拷贝数。共济失调-毛细血管扩张突变（ATM）激活和大T抗原（LTag）表达的免疫荧光分析清楚地表明，在感染后1天的AVP治疗将生产性SV40复制的发生延迟了大约3天，并且相对于用媒介物治疗的患者，感染的发生受到了很大的限制控件。AVP剂量反应实验记录的IC50在低nM范围内，与先前报道的HPV16的IC50相似。接下来检查了AVP对BKPyV起作用的能力。再次，除AVP（PA1）对BKPyV Dunlop菌株的IC50为437 nM外，获得了低nM范围内的IC50。Mre11抑制剂Mirin大大降低了针对SV40的AVP IC50，表明Mre11保护PyV基因组免受AVP作用，如先前对HPV所示。这些实验共同表明，AVP是有效的PyV抗病毒药，其作用机制与HPV相似。结果表明，AVP是控制和研究PyV生物学的有用工具。这些试剂针对BKPyV和其他PyV病原体的潜在用途也具有临床意义。Mre11抑制剂Mirin大大降低了针对SV40的AVP IC50，表明Mre11保护PyV基因组免受AVP作用，如先前对HPV所示。这些实验共同表明，AVP是有效的PyV抗病毒药，其作用机制与HPV相似。结果表明，AVP是控制和研究PyV生物学的有用工具。这些试剂针对BKPyV和其他PyV病原体的潜在用途也具有临床意义。Mre11抑制剂Mirin大大降低了针对SV40的AVP IC50，表明Mre11保护PyV基因组免受AVP作用，如先前对HPV所示。这些实验共同表明，AVP是有效的PyV抗病毒药，其作用机制与HPV相似。结果表明，AVP是控制和研究PyV生物学的有用工具。这些试剂针对BKPyV和其他PyV病原体的潜在用途也具有临床意义。