关键词: anti-viral antimicrobial peptide human viruses infection resistance

Mesh : Animals Antiviral Agents / pharmacology Anura Anti-Inflammatory Agents / pharmacology Herpesvirus 1, Human / drug effects Amphibian Proteins / pharmacology Peptides / pharmacology Vero Cells Chlorocebus aethiops

来  源:   DOI:10.1093/jambio/lxae165

Abstract:
OBJECTIVE: The high incidence of virus-related infections and the large diffusion of drug-resistant pathogens stimulate the search and identification of new antiviral agents with a broad spectrum of action. Antivirals can be designed to act on a single target by interfering with a specific step in the viral lifecycle. On the contrary, antiviral peptides (AVPs) are known for acting on a wide range of viruses, with a diversified mechanism of action targeting virus and/or host cell. In the present study, we evaluated the antiviral potential of the peptide Hylin-a1 secreted by the frog Hypsiobas albopunctatus against members of the Herpesviridae family.
RESULTS: The inhibitory capacity of the peptide was evaluated in vitro by plaque assays in order to understand the possible mechanism of action. The results were also confirmed by real-time PCR and Western blot evaluating the expression of viral genes. Hylin-a1 acts to block the herpetic infection interfering at the early stages of both herpes simplex virus type 1 (HSV-1) and type 2 infection. Its mechanism is mainly directed on the membrane, probably by damaging the viral envelope. The same effect was also observed against HSV-1 strains resistant to acyclovir.
CONCLUSIONS: The data presented in this study, such as the increased activity of the peptide when combined to acyclovir, a weak hemolytic profile, an anti-inflammatory effect, and a tolerable half-life in serum, indicates Hylin-a1 as a novel antiherpetic molecule with promising potential in the clinical setting.
摘要:
目的:病毒相关性感染的高发生率和耐药病原菌的大量扩散,促使人们寻找和鉴定具有广谱作用的新型抗病毒药物。可以将抗病毒剂设计为通过干扰病毒生命周期中的特定步骤而作用于单个靶标。相反,已知抗病毒肽(AVPs)作用于多种病毒,具有靶向病毒和/或宿主细胞的多种作用机制。在本研究中,我们评估了青蛙Hypsiobasalbopunctatus分泌的肽Hylin-a1对疱疹病毒科成员的抗病毒潜力。
结果:为了了解可能的作用机制,通过空斑测定法在体外评估了肽的抑制能力。通过实时PCR和Western印迹评估病毒基因的表达也证实了该结果。Hylin-a1可在1型单纯疱疹病毒(HSV-1)和2型(HSV-2)感染的早期阻止疱疹感染。其机制主要针对膜,可能是通过破坏病毒包膜。对对阿昔洛韦具有抗性的HSV-1菌株也观察到相同的效果。
结论:本研究中提供的数据,例如,当与阿昔洛韦结合时,肽的活性增加,微弱的溶血特征,抗炎作用,在血清中具有可耐受的半衰期,表明Hylin-a1是一种新型的抗疱疹分子,在临床上具有广阔的潜力。
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