title: Targeting the retroviral ribonuclease H by rational drug design.
abstract: Ribonucleases H or RNases H are conserved and exist in almost every organism. They generate and remove RNA primers, which are required for DNA replication. RNases H hydrolyze RNA in RNA-DNA hybrids. RNases H and related enzymes contribute to reduction of gene expression in antisense and small-interfering RNA mechanisms for gene silencing. Retroviruses code for RNases H, which are required for DNA provirus synthesis. Their RNase H is fused to the reverse transcriptase and essential for virus replication inside the cell. Retroviruses code for four enzymes, three of which have been targeted by antiretroviral therapies. A drug against the fourth one, the retroviral RNase H, does not yet exist. The viral but not cellular RNases H should be targeted by drug design. Some details will be discussed here. Furthermore, a compound is described, which enables the RNase H to kill cell-free HIV particles by driving the virus into suicide - with potential use as a microbicide.
authors.affiliation: Institute for Medical Microbiology, University of Zurich, Zurich, Switzerland. moelling@molgen.mpg.de
authors.forename: Karin
authors.initials: K
authors.lastname: Moelling
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000494:pharmacology*; D004261:DNA Replication; D015195:Drug Design; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D020868:Gene Silencing; D054303:HIV Reverse Transcriptase / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D009154:Mutation; D021141:Nucleic Acid Amplification Techniques; D012367:RNA, Viral / Q000187:drug effects*; D016914:Ribonuclease H / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics*
chemical_list: D000890:Anti-Infective Agents; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D016914:Ribonuclease H