Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, 41121 Modena, Italy.
Clinical and Experimental Medicine Ph.D. Program, University of Modena and Reggio Emilia, 41121 Modena, Italy.
Int J Mol Sci. 2024 Oct 1;25(19):10602. doi: 10.3390/ijms251910602.
Antimicrobial peptides represent a promising alternative to traditional drugs in relation to cost, toxicity, and, primarily, the growing problem of drug resistance. Here, we report on the activity against HSV-1 and HSV-2 of a previously described wide-spectrum synthetic decapeptide, Killer Peptide (KP). As determined by plaque reduction assays, treatment with KP at 100 μg/mL resulted in a reduction in the viral yield titer of 3.5 Logs for HSV-1 and 4.1 Logs for HSV-2. Further evaluation of KP antiviral activity focused on the early stages of the virus replicative cycle, including the determination of the residual infectivity of viral suspensions treated with KP. A direct effect of the peptide on viral particles impairing virus absorption and penetration was shown. The toxicity profile proved to be extremely good, with a selectivity index of 29.6 for HSV-1 and 156 for HSV-2. KP was also active against acyclovir (ACV)-resistant HSV isolates, while HSV subcultures in the presence of sub-inhibitory doses of KP did not lead to the emergence of resistant strains. Finally, the antiviral action of KP proved to be synergistic with that of ACV. Overall, these results demonstrate that KP could represent an interesting addition/alternative to acyclovir for antiviral treatment.
抗菌肽在成本、毒性方面,尤其是在日益严重的耐药问题上,代表了传统药物的一种有前途的替代选择。在这里,我们报告了先前描述的广谱合成十肽 Killer Peptide(KP)对 HSV-1 和 HSV-2 的活性。通过蚀斑减少测定法确定,用 100μg/mL 的 KP 处理可使 HSV-1 的病毒产量滴度降低 3.5 对数,使 HSV-2 的病毒产量滴度降低 4.1 对数。对 KP 抗病毒活性的进一步评估集中在病毒复制周期的早期阶段,包括确定用 KP 处理的病毒悬浮液的残留感染性。表明该肽对病毒颗粒具有直接作用,可损害病毒的吸收和穿透。毒性概况非常好,对 HSV-1 的选择性指数为 29.6,对 HSV-2 的选择性指数为 156。KP 对阿昔洛韦(ACV)耐药的 HSV 分离株也有效,而在亚抑制剂量的 KP 存在下进行 HSV 亚培养不会导致耐药株的出现。最后,KP 的抗病毒作用与 ACV 的作用协同。总体而言,这些结果表明 KP 可能是抗病毒治疗中替代 ACV 的一种有趣选择。