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Título: | Ribonuclease H, an unexploited target for antiviral intervention against HIV and hepatitis B virus |
Autor: | Tramontano, Enzo; Corona, Angela; Menéndez-Arias, Luis CSIC ORCID | Palabras clave: | Ribonuclease H Reverse transcriptase HIV Hepatitis B virus Antiviral |
Fecha de publicación: | 21-sep-2019 | Citación: | Antiviral Research 171 (2019) | Resumen: | 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. | Versión del editor: | http://dx.doi.org/10.1016/j.antiviral.2019.104613 | URI: | http://hdl.handle.net/10261/228608 | DOI: | 10.1016/j.antiviral.2019.104613 | Identificadores: | doi: 10.1016/j.antiviral.2019.104613 issn: 1872-9096 |
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