A5058945322- Hepatitis B Virus Studies
- Hepatitis C virus research
- Viral gastroenteritis research and epidemiology
- HIV/AIDS drug development and treatment
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- Protein Structure and Dynamics
- Chronic Lymphocytic Leukemia Research
- Cancer-related Molecular Pathways
- Liver Disease Diagnosis and Treatment
Saint Louis University
2017-2022
Chronic hepatitis B virus infection cannot be cured by current therapies, so new treatments are urgently needed. We recently identified novel inhibitors of the ribonuclease H that suppress viral replication in cell culture. Here, we employed immunodeficient FRG KO mice whose livers had been engrafted with primary human hepatocytes to ask whether can vivo. Humanized infected were treated for two weeks #110, an α-hydroxytropolone, and #208, N-hydroxypyridinedione. Hepatitis titers S e antigen...
Hepatitis B virus (HBV) chronically infects >250 million people. It replicates by a unique protein-primed reverse transcription mechanism, and the primary anti-HBV drugs are nucleos(t)ide analogs targeting viral polymerase (P). P has four domains compared to only two in most transcriptases: terminal protein (TP) that primes DNA synthesis, spacer, transcriptase (RT), ribonuclease H (RNase H). Despite being major drug target catalyzing pathway very different from retroviruses, HBV resisted...
The α-hydroxytropolones (αHTs) are troponoid inhibitors of hepatitis B virus (HBV) replication that can target HBV RNase H with submicromolar efficacies. αHTs and related troponoids (tropones tropolones) be cytotoxic in cell lines as measured by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 -tetrazolium (MTS) assays assess mitochondrial function. Previous studies suggest tropolones induce cytotoxicity through inhibition respiration.
The ribonucleases H (RNases H) of HIV and hepatitis B virus are type 1 RNases that promising drug targets because inhibiting their activity blocks viral replication. Eukaryotic ribonuclease H1 (RNase H1) is an essential protein a probable off-target enzyme for RNase inhibitors. α-hydroxytropolones (αHTs) class anti-RNase inhibitors can inhibit the HIV, virus, human H1; however, it unclear how these could be developed to distinguish between enzymes. To accelerate development selective...
Abstract Hepatitis B virus (HBV) replicates by protein-primed reverse transcription. It chronically infects >250 million people, and the dominant anti-HBV drugs are nucleos(t)ide analogs targeting viral polymerase (P). P has four domains, terminal protein (TP) that primes DNA synthesis, a spacer, transcriptase (RT), ribonuclease H (RNaseH). Despite being major drug target catalyzing transcription pathway very different from retroviral pathway, HBV resisted structural analysis for decades....
Human immunodeficiency virus (HIV) and Hepatitis B (HBV) ribonucleases H (RNase H) are type 1 RNases that promising drug targets because inhibiting their activity blocks viral replication. cleave RNA in RNA/DNA hybrids. Eukaryotic RNase H1 is an essential protein probable off-target enzyme for inhibitors. α-hydroxytropolones (αHTs) comprise anti-RNase inhibitor class can inhibit the HIV, HBV, human H1. These compounds work by binding active site chelating catalytic divalent metal cofactors....