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1-二十二醇(一种包括单纯疱疹病毒在内的脂包膜病毒抑制剂)的抗病毒活性

Antiviral activity of 1-docosanol, an inhibitor of lipid-enveloped viruses including herpes simplex.

作者信息

Katz D H, Marcelletti J F, Khalil M H, Pope L E, Katz L R

机构信息

LIDAK Pharmaceuticals, La Jolla, CA.

出版信息

Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10825-9. doi: 10.1073/pnas.88.23.10825.

Abstract

This article reports that 1-docosanol, a 22-carbon-long saturated alcohol, exerts a substantial inhibitory effect on replication of certain viruses (e.g., herpes simplex virus and respiratory syncytial virus) within primary target cells in vitro. To study the basis for its viral inhibitory activity, a suspension of 1-docosanol was formulated in an inert and nontoxic surfactant, Pluronic F-68; this suspension exerted potent inhibitory activity on the ability of susceptible viruses to infect cultured target cells. Susceptible viruses included wild-type herpes simplex viruses 1 and 2 as well as acyclovir-resistant herpes simplex virus 2 and also respiratory syncytial virus--all of which are lipid-enveloped. In contrast, nonenveloped poliovirus was not susceptible to the inhibitory action of 1-docosanol. Although the precise mechanism has yet to be defined, current evidence suggests that 1-docosanol inhibits viral replication by interfering with the early intracellular events surrounding viral entry into target cells. It is possible that interaction between the highly lipophilic compound and components of target cell membranes renders such target cells less susceptible to viral fusion and/or entry. If this mechanism proves to be correct, 1-docosanol may provide a broad spectrum activity against many different viruses, especially those with lipid-containing envelopes.

摘要

本文报道,1-二十二醇(一种含有22个碳原子的饱和醇)在体外对原代靶细胞内的某些病毒(如单纯疱疹病毒和呼吸道合胞病毒)复制具有显著抑制作用。为研究其病毒抑制活性的基础,将1-二十二醇悬浮于惰性无毒表面活性剂普朗尼克F-68中;该悬浮液对易感病毒感染培养靶细胞的能力具有强大抑制活性。易感病毒包括野生型单纯疱疹病毒1型和2型、阿昔洛韦耐药的单纯疱疹病毒2型以及呼吸道合胞病毒——所有这些病毒均为脂质包膜病毒。相比之下,无包膜的脊髓灰质炎病毒对1-二十二醇的抑制作用不敏感。尽管确切机制尚未明确,但目前证据表明,1-二十二醇通过干扰病毒进入靶细胞周围的早期细胞内事件来抑制病毒复制。高度亲脂性化合物与靶细胞膜成分之间的相互作用可能使此类靶细胞对病毒融合和/或进入的敏感性降低。如果这一机制被证明是正确的,1-二十二醇可能对许多不同病毒具有广谱活性,尤其是那些含有脂质包膜的病毒。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d22/53024/2b9261cbcd4b/pnas01073-0461-a.jpg

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