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两种合成两亲性肽和蛙皮素-2对1型和2型单纯疱疹病毒的活性。

Activity of two synthetic amphiphilic peptides and magainin-2 against herpes simplex virus types 1 and 2.

作者信息

Aboudy Y, Mendelson E, Shalit I, Bessalle R, Fridkin M

机构信息

Central Virology Laboratory, Chaim Sheba Medical Center, Tel Hashomer, Israel.

出版信息

Int J Pept Protein Res. 1994 Jun;43(6):573-82. doi: 10.1111/j.1399-3011.1994.tb00559.x.

Abstract

The in vitro antiviral activity of two amphiphilic synthetic peptides, modelin-1 (mod-1) and modelin-5 (mod-5), and of the natural antibacterial peptide magainin-2 (mag-2) against herpes simplex viruses type 1 (HSV-1) and 2 (HSV-2) were evaluated. The peptides were incubated with the virus, i.e. direct inactivation, and their effects examined by means of plaque reduction assay and/or reduction in virus yield. Only mod-1 displayed a strong antiviral effect against HSV-1 and HSV-2, with 50% effective dose (ED50) values of 4.6 and 4.1 micrograms/mL, respectively. Mag-2, mod-5 and a mixture of both had no significant inhibitory effect. Addition of mod-1 up to a concentration of 100 micrograms/mL to the culture medium had no significant cytotoxic effect on host vero cells, as measured by the trypan blue-exclusion method. It showed, however, considerable hemolytic activity against human red blood cells. Experiments including acyclovir (ACV) as a reference viral inhibitor indicated that the mode of action of mod-1 is different from that of ACV. In contrast to ACV, the peptide inactivates the virus following a very short incubation before vero cell infection, suggesting some kind of direct interaction of the peptide with the viral envelope, rather than inhibition of viral DNA replication or gene expression. Our results suggest that mod-1 may be an effective topical antiviral agent against herpes viruses.

摘要

评估了两种两亲性合成肽(模拟素-1(mod-1)和模拟素-5(mod-5))以及天然抗菌肽马盖宁-2(mag-2)对1型单纯疱疹病毒(HSV-1)和2型单纯疱疹病毒(HSV-2)的体外抗病毒活性。将这些肽与病毒一起孵育,即直接灭活,并通过蚀斑减少试验和/或病毒产量降低来检测其效果。只有mod-1对HSV-1和HSV-2显示出强大的抗病毒作用,其50%有效剂量(ED50)值分别为4.6和4.1微克/毫升。Mag-2、mod-5以及两者的混合物均无显著抑制作用。通过台盼蓝排斥法测定,向培养基中添加浓度高达100微克/毫升的mod-1对宿主 vero 细胞没有显著的细胞毒性作用。然而,它对人红细胞显示出相当大的溶血活性。包括阿昔洛韦(ACV)作为参考病毒抑制剂的实验表明,mod-1的作用方式与ACV不同。与ACV相反,该肽在 vero 细胞感染前经过非常短的孵育后就能使病毒失活,这表明该肽与病毒包膜存在某种直接相互作用,而不是抑制病毒DNA复制或基因表达。我们的结果表明,mod-1可能是一种有效的抗疱疹病毒局部抗病毒剂。

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