ArticleAntimicrobial agents and chemotherapy2012
Structural and inhibition studies of the RNase H function of xenotropic murine leukemia virus-related virus reverse transcriptase.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Development of Human Immunodeficiency Virus Type 1 Resistance to 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine Starting with Wild-Type or Nucleoside Reverse Transcriptase Inhibitor-Resistant Strains.Antimicrobial agents and chemotherapy · 2021Trial
- HIV-1 Reverse Transcriptase/Integrase Dual Inhibitors: A Review of Recent Advances and Structure-activity Relationship Studies.Iranian journal of pharmaceutical research : IJPR · 2021Review
- Effect of P-body component Mov10 on HCV virus production and infectivity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Determinants of Active-Site Inhibitor Interaction with HIV-1 RNase H.ACS infectious diseases · 2019Article
- Article
- Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H.European journal of medicinal chemistry · 2017Article
- A 2-Hydroxyisoquinoline-1,3-Dione Active-Site RNase H Inhibitor Binds in Multiple Modes to HIV-1 Reverse Transcriptase.Antimicrobial agents and chemotherapy · 2017Article
- 3-Hydroxypyrimidine-2,4-Diones as Novel Hepatitis B Virus Antivirals Targeting the Viral Ribonuclease H.Antimicrobial agents and chemotherapy · 2017Article
- 6-Cyclohexylmethyl-3-hydroxypyrimidine-2,4-dione as an inhibitor scaffold of HIV reverase transcriptase: Impacts of the 3-OH on inhibiting RNase H and polymerase.European journal of medicinal chemistry · 2017Article
- Structural basis of suppression of host translation termination by Moloney Murine Leukemia Virus.Nature communications · 2016Article
- Design, Synthesis, and Biological Evaluations of Hydroxypyridonecarboxylic Acids as Inhibitors of HIV Reverse Transcriptase Associated RNase H.Journal of medicinal chemistry · 2016Article
- A hybrid chimeric system for versatile and ultra-sensitive RNase detection.Scientific reports · 2015Article
- Design, synthesis, biochemical, and antiviral evaluations of C6 benzyl and C6 biarylmethyl substituted 2-hydroxylisoquinoline-1,3-diones: dual inhibition against HIV reverse transcriptase-associated RNase H and polymerase with antiviral activities.Journal of medicinal chemistry · 2015Article
- Inhibition of the ANT(2")-Ia resistance enzyme and rescue of aminoglycoside antibiotic activity by synthetic α-hydroxytropolones.Bioorganic & medicinal chemistry letters · 2014Article
- 4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) inhibits HIV-1 reverse transcriptase with multiple mechanisms.The Journal of biological chemistry · 2014Article
- The biology and synthesis of α-hydroxytropolones.MedChemComm · 2014Article
- Evidence from molecular dynamics simulations of conformational preorganization in the ribonuclease H active site.F1000Research · 2014Article
- Evaluation of Combinations of 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine with Clinically Used Antiretroviral Drugs.Antimicrobial agents and chemotherapy · 2013Article
- Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA.Retrovirology · 2013Article
- Structural analysis of monomeric retroviral reverse transcriptase in complex with an RNA/DNA hybrid.Nucleic acids research · 2013Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
RNase H inhibitors (RNHIs) have gained attention as potential HIV-1 therapeutics. Although several RNHIs have been studied in the context of HIV-1 reverse transcriptase (RT) RNase H, there is no information on inhibitors that might affect the RNase H activity of other RTs. We performed biochemical, virological, crystallographic, and molecular modeling studies to compare the RNase H function and inhibition profiles of the gammaretroviral xenotropic murine leukemia virus-related virus (XMRV) and Moloney murine leukemia virus (MoMLV) RTs to those of HIV-1 RT. The RNase H activity of XMRV RT is significantly lower than that of HIV-1 RT and comparable to that of MoMLV RT. XMRV and MoMLV, but not HIV-1 RT, had optimal RNase H activities in the presence of Mn²⁺ and not Mg²⁺. Using hydroxyl-radical footprinting assays, we demonstrated that the distance between the polymerase and RNase H domains in the MoMLV and XMRV RTs is longer than that in the HIV-1 RT by ∼3.4 Å. We identified one naphthyridinone and one hydroxyisoquinolinedione as potent inhibitors of HIV-1 and XMRV RT RNases H with 50% inhibitory concentrations ranging from ∼0.8 to 0.02 μM. Two acylhydrazones effective against HIV-1 RT RNase H were less potent against the XMRV enzyme. We also solved the crystal structure of an XMRV RNase H fragment at high resolution (1.5 Å) and determined the molecular details of the XMRV RNase H active site, thus providing a framework that would be useful for the design of antivirals that target RNase H.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.