Ribonuclease H, an unexploited target for antiviral intervention against HIV and hepatitis B virus.

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ID: 86353
2019
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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-hydroxyisoquinolinediones 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 inhibitory activity, broad specificity and efforts to decrease their toxicity.
Reference Key
tramontano2019ribonucleaseantiviral Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Tramontano, Enzo;Corona, Angela;Menéndez-Arias, Luis;
Journal Antiviral research
Year 2019
DOI
S0166-3542(19)30493-0
URL
Keywords
hiv antiviral hepatitis b virus reverse transcriptase ribonuclease h

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