PDF(Pubmed)
Abstract：
Although antimicrobial peptides have been shown to inactivate viruses through disruption of their viral envelopes, clinical use of such peptides has been hampered by a number of factors, especially their enzymatically unstable structures. To overcome the shortcomings of antimicrobial peptides, peptoids (sequence-specific N-substituted glycine oligomers) mimicking antimicrobial peptides have been developed. We aimed to demonstrate the antiviral effects of antimicrobial peptoids against hepatitis B virus (HBV) in cell culture. The anti-HBV activity of antimicrobial peptoids was screened and evaluated in an infection system involving the HBV reporter virus and HepG2.2.15-derived HBV. By screening with the HBV reporter virus infection system, three (TM1, TM4, and TM19) of 12 peptoids were identified as reducing the infectivity of HBV, though they did not alter the production levels of HBs antigen in cell culture. These peptoids were not cytotoxic at the evaluated concentrations. Among these peptoids, TM19 was confirmed to reduce HBV infection most potently in a HepG2.2.15-derived HBV infection system that closely demonstrates authentic HBV infection. In cell culture, the most effective administration of TM19 was virus treatment at the infection step, but the reduction in HBV infectivity by pre-treatment or post-treatment of cells with TM19 was minimal. The disrupting effect of TM19 targeting infectious viral particles was clarified in iodixanol density gradient analysis. In conclusion, the peptoid TM19 was identified as a potent inhibitor of HBV. This peptoid prevents HBV infection by disrupting viral particles and is a candidate for a new class of anti-HBV reagents.
摘要：
尽管抗菌肽已被证明可以通过破坏病毒包膜来灭活病毒，这些肽的临床应用受到许多因素的阻碍，尤其是酶的不稳定结构.为了克服抗菌肽的缺点，已经开发了模拟抗微生物肽的类肽（序列特异性N-取代的甘氨酸寡聚物）。我们的目的是证明抗微生物肽抗乙型肝炎病毒（HBV）在细胞培养的抗病毒作用。在涉及HBV报告病毒和HepG2.2.15衍生的HBV的感染系统中筛选和评估抗微生物肽的抗HBV活性。通过HBV报告病毒感染系统的筛查，3（TM1，TM4和TM19）的12个肽被确定为降低HBV的感染性，尽管它们没有改变细胞培养物中HBs抗原的产生水平。这些类肽在评估的浓度下没有细胞毒性。在这些拟肽中，TM19被证实在HepG2.2.15衍生的HBV感染系统中最有效地减少HBV感染，该系统密切证明了真实的HBV感染。在细胞培养中,TM19最有效的给药是感染步骤的病毒治疗，但用TM19治疗前或后处理细胞对HBV感染性的降低是最小的。在碘克沙醇密度梯度分析中阐明了TM19靶向感染性病毒颗粒的破坏作用。总之,类肽TM19被确定为HBV的有效抑制剂。这种类肽通过破坏病毒颗粒来预防HBV感染，并且是一类新型抗HBV试剂的候选者。
