Safety, formulation, and in vitro antiviral activity of the antimicrobial peptide subtilosin against herpes simplex virus type 1.

Safety, formulation, and in vitro antiviral activity of the antimicrobial peptide subtilosin against herpes simplex virus type 1.
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DOI:
10.1007/s12602-012-9123-x
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发表时间:
2013-03-01
影响因子:
4.9
通讯作者:
Chikindas, Michael L.
Chikindas, Michael L.
中科院分区:
工程技术2区
文献类型:
--
作者:
Torres, Nicolas I.;Noll, Katia Sutyak;Xu, Shiqi;Li, Ji;Huang, Qingrong;Sinko, Patrick J.;Wachsman, Monica B.;Chikindas, Michael L.

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在本研究中,细菌素subtilosin对单纯疱疹病毒1型(HSV-1)的抗病毒特性和安全性和有效性的subtilosin为基础的抗病毒制剂进行了测定。高浓度的枯草杆菌素,由解淀粉芽孢杆菌产生的环状抗菌肽,对HSV-1具有杀病毒作用。有趣的是,在非杀病毒浓度下,subtilosin以剂量依赖性方式抑制野生型HSV-1和阿昔洛韦抗性突变体。虽然确切的抗病毒机制尚未完全了解,添加时间实验和蛋白质印迹分析表明,subtilosin不影响蛋白质合成前的病毒增殖步骤。采用静电纺丝法制备了宽度为278 nm的聚乙烯醇(PVOH)基枯草杆菌素纳米纤维。通过琼脂孔扩散测定法测定基于枯草杆菌素的纤维的保留的抗微生物活性。纤维的负载量为2.4mg/g纤维,负载效率为31.6%。此外,使用体外人组织模型,显示掺入和不掺入枯草杆菌素的纳米纤维对人表皮组织无毒。综合这些结果,基于枯草杆菌素的纳米纤维应该作为治疗和/或控制HSV-1感染的新的替代方法进行进一步研究。
In the present study the antiviral properties of the bacteriocin subtilosin against Herpes simplex virus type 1 (HSV-1) and the safety and efficacy of a subtilosin-based nanofiber formulation were determined. High concentrations of subtilosin, the cyclical antimicrobial peptide produced by Bacillus amyloliquefaciens, were virucidal against HSV-1. Interestingly, at non-virucidal concentrations, subtilosin inhibited wild type HSV-1 and aciclovir-resistant mutants in a dose-dependent manner. Although the exact antiviral mechanism is not fully understood, time of addition experiments and western blot analysis suggest that subtilosin does not affect viral multiplication steps prior to protein synthesis. Poly(vinyl alcohol) (PVOH)-based subtilosin nanofibers with a width of 278 nm were produced by the electrospinning process. The retained antimicrobial activity of the subtilosin-based fibers was determined via an agar well diffusion assay. The loading capacity of the fibers was 2.4 mg subtilosin/g fiber, and loading efficiency was 31.6%. Furthermore, the nanofibers with and without incorporated subtilosin were shown to be nontoxic to human epidermal tissues using an in vitro human tissue model. Taking together these results subtilosin-based nanofibers should be further studied as a novel alternative method for treatment and/or control of HSV-1 infection.
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