核糖核酸酶H，针对HIV和乙肝病毒的抗病毒干预药物，尚未开

StephenW

Antiviral Res. 2019 Sep 21:104613. doi: 10.1016/j.antiviral.2019.104613. [Epub ahead of print]
Ribonuclease H, an unexploited target for antiviral intervention against HIV and hepatitis B virus.
Tramontano E1, Corona A2, Menendez-Arias L3.
Author information

1
    Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy. Electronic address: [email protected].
2
    Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
3
    Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas & Universidad Autónoma de Madrid), Madrid, Spain. Electronic address: [email protected].

Abstract

Ribonucleases H (RNases H) are endonucleolytic enzymes, evolutionarily related to retroviral integrases, DNA transposases, resolvases and numerous nucleases. RNases H cleave RNA in RNA/DNA hybrids and their activity plays an important role in the replication of prokaryotic and eukaryotic genomes, as well as in the replication of reverse-transcribing viruses. During reverse transcription, the RNase H activity of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) degrades the viral genomic RNA to facilitate the synthesis of viral double-stranded DNA. HIV and HBV reverse transcriptases contain DNA polymerase and RNase H domains that act in a coordinated manner to produce double-stranded viral DNA. Although RNase H inhibitors have not been developed into licensed drugs, recent progress has led to the identification of a number of small molecules with inhibitory activity at low micromolar or even nanomolar concentrations. These compounds can be classified into metal-chelating active site inhibitors and allosteric inhibitors. Among them, α-hydroxytropolones, N-hydroxyixoquinolinediones and N-hydroxypyridinediones represent chemotypes active against both HIV and HBV RNases H. In this review we summarize recent developments in the field including the identification of novel RNase H inhibitors, compounds with dual activity, broad specificity and efforts to decrease their toxicity.

Copyright © 2019. Published by Elsevier B.V.
KEYWORDS:

Antiviral; HIV; Hepatitis B virus; Reverse transcriptase; Ribonuclease H

PMID:
    31550450
DOI:
    10.1016/j.antiviral.2019.104613

StephenW

抗病毒水库。 2019年9月21日：104613。 doi：10.1016 / j.antiviral.2019.104613。 [Epub提前发布]
核糖核酸酶H，针对HIV和乙肝病毒的抗病毒干预药物，尚未开发。
Tramontano E1，Corona A2，Menendez-Arias L3。
作者信息

1
    卡利亚里大学生命与环境科学系，意大利卡利亚里。电子地址：[email protected]。
2
    卡利亚里大学生命与环境科学系，意大利卡利亚里。
3
    分子生物学中心“ Severo Ochoa”（西班牙体育研究中心和马德里自治大学），马德里，西班牙。电子地址：[email protected]。

抽象

核糖核酸酶H（RNases H）是内切核酸酶，在进化上与逆转录病毒整合酶，DNA转座酶，分离酶和许多核酸酶有关。 RNases H切割RNA / DNA杂种中的RNA，它们的活性在原核和真核基因组的复制以及逆转录病毒的复制中起重要作用。在逆转录过程中，人类免疫缺陷病毒（HIV）和乙型肝炎病毒（HBV）的RNase H活性会降解病毒基因组RNA，从而促进病毒双链DNA的合成。 HIV和HBV逆转录酶含有DNA聚合酶和RNase H结构域，它们以协调的方式起作用，以产生双链病毒DNA。尽管RNase H抑制剂尚未开发为许可药物，但最近的进展已导致鉴定出许多在低微摩尔甚至纳摩尔浓度下具有抑制活性的小分子。这些化合物可分为金属螯合活性位点抑制剂和变构抑制剂。其中，α-羟基营养激素，N-羟基ixo喹啉二酮和N-羟基吡啶二酮代表对HIV和HBV RNases H均具有活性的化学型。特异性并努力降低其毒性。

版权所有©2019.由Elsevier B.V.发布
关键词：

抗病毒; HIV;乙型肝炎病毒；逆转录酶；核糖核酸酶H

结论：
    31550450
DOI：
    10.1016 / j.antiviral.2019.104613