Chronic Hepatitis B virus (HBV) infection is a major worldwide public health problem. Current direct-acting anti-HBV drugs target the HBV DNA polymerase activity, but the equally essential viral ribonuclease H (RNaseH) activity is unexploited as a drug target. Previously, we reported that α-hydroxytropolone compounds can inhibit the HBV RNaseH and block viral replication. Subsequently, we found that our biochemical RNaseH assay underreports efficacy of the α-hydroxytropolones against HBV replication. Therefore, we conducted a structure-activity analysis of 59 troponoids against HBV replication in cell culture. These studies revealed that antiviral efficacy is diminished by larger substitutions on the tropolone ring, identified key components in the substitutions needed for high efficacy, and revealed that cytotoxicity correlates with increased lipophilicity of the α-hydroxytropolones. These data provide key guidance for further optimization of the α-hydroxytropolone scaffold as novel HBV RNaseH inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549669 | PMC |
| http://dx.doi.org/10.1016/j.antiviral.2017.06.014 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Effect of c-Myb overexpression on osteoblastic-, odontoblastic-, and cementoblastic differentiation of primary human periodontal ligament cells.
Eur J Oral Sci
January 2025
Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Jeonbuk National University, Jeonju-si, South Korea.
The periodontal ligament (PDL) is a connective tissue, and PDL cells have a potential to differentiate into cementoblasts, osteoblasts, and gingival fibroblasts. This study investigated whether transcription factor c-Myb could induce differentiation of PDL cells for periodontal regeneration. PDL cells were isolated from extracted teeth and cultured.
View Article and Find Full Text PDFModeling the response to interleukin-21 to inform natural killer cell immunotherapy.
Immunol Cell Biol
January 2025
Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA.
Natural killer (NK) cells are emerging agents for cancer therapy. Several different cytokines are used to generate NK cells for adoptive immunotherapy including interleukin (IL)-2, IL-12, IL-15 and IL-18 in solution, and membrane-bound IL-21. These cytokines drive NK cell activation through the integration of signal transducers and activators of transcription (STAT) and nuclear factor-kappa B (NF-κB) pathways, which overlap and synergize, making it challenging to predict optimal cytokine combinations for both proliferation and cytotoxicity.
View Article and Find Full Text PDFA 3D Cell-Culture System That Uses Nano-Fibrillated Bacterial Cellulose to Prepare a Spherical Formulation of Culture Cells.
Biol Pharm Bull
January 2025
Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8505, Japan.
A 3-dimensional (3D) cell culture is now being actively pursued to accomplish the in vivo-like cellular morphology and biological functions in cell culture. We recently obtained nano-fibrillated bacterial cellulose (NFBC). In this study, we developed a novel NFBC-based 3D cell-culture system, the OnGel method, and the Suspension method.
View Article and Find Full Text PDFHypoxia-regulated miR-103-3p/FGF2 axis in adipose-derived stem cells promotes angiogenesis by vascular endothelial cells during ischemic tissue repair.
Int J Cardiol
January 2025
Department of Plastic Surgery, The First Affiliated Hospital of Jinan University, Key Laboratory of Regenerative Medicine, Ministry of Education, Guangzhou, Guangdong Province 510630, China. Electronic address:
Background: Identifying factors mediating adipose-derived stem cells (ADSCs)-induced endothelial cell angiogenesis in hypoxic skin flap tissue is critical for reconstruction. While the paracrine action of VEGF by adipose-derived stem cells (ADSCs) is established in promoting endothelial cell angiogenesis, the role of FGF2 and its regulatory mechanisms in ADSCs paracrine secretion remains unclear.
Methods: We induced hypoxia and examined the expression level of FGF2 in ADSCs using ELISA, qRT-PCR, and western blotting.
Genomic evolution of SARS-CoV-2 in Morocco: Insights from Whole Genome Sequences collected from 2020 to 2024.
Virus Res
January 2025
Molecular Biology and Functional Genomics Platform, National Centre for Scientific and Technical Research (CNRST), Rabat, Morocco; Genomic Centre for Human Pathologies (GENOPATH), Neuroscience and Neurogenetics Research Team, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat, Morocco. Electronic address:
This study investigates the evolution and genetic diversity of SARS-CoV-2 strains circulating in Morocco to track the spread, clade distributions and mutations of the virus across various regions from February 2020 to June 2024. The genome sequences were retrieved from the GISAID database. A total of 2630 SARS-CoV-2 genome sequences were analyzed using bioinformatic tools such as Nextclade, followed by phylogenetic and statistical analyses.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!