Most cited article - PubMed ID 27036553
Protective hybrid coating containing silver, copper and zinc cations effective against human immunodeficiency virus and other enveloped viruses
PURPOSE: The aim of this study was to evaluate the antibacterial efficacy of surface-treated hernia implants modified by a hybrid nanolayer with incorporated Ag, Cu, and Zn cations using the sol-gel method. METHODS: The materials (polypropylene, polyester, and polyvinylidene difluoride) were activated by vacuum plasma treatment or UV C radiation, then modified and tested for bacterial strains of Escherichia coli (gram-negative) and Staphylococcus aureus (gram-positive). The AATCC 100 (2019) method for quantitative and the ISO 20645 agar plate propagation method for qualitative evaluation of microbiological efficacy were used. The gradual release of incorporated ions was monitored over time in simulated body fluids (blood plasma, peritoneal fluid) and physiological saline using an inductively coupled plasma mass spectrometer. The thickness and the homogeneity of the layers were measured for individual random samples with scanning electron microscope analysis (SEMA) and evaluated with an elemental analysis. RESULTS: Qualitative and quantitative microbiological tests clearly show the great suitability of vacuum plasma and UV C with sol AD30 (dilution 1:1) surface treatment of the implants. The absolute concentration of Ag, Cu, and Zn cations in leachates was very low. SEMA showed a high degree of homogeneity of the layer and only very rare nanocracks by all tested materials appear after mechanical stress. CONCLUSION: This study confirms that surface treatment of meshes using the sol-gel method significantly increases the antibacterial properties. The nanolayers are sufficiently mechanically resistant and stable and pose no threat to health.
- Keywords
- Antibacterial agent, Scanning electron microscopy, Sol gel, Surface, Surgical mesh,
- Publication type
- Journal Article MeSH
The secondary structure of nucleic acids containing quartets of guanines, termed G-quadruplexes, is known to regulate the transcription of many genes. Several G-quadruplexes can be formed in the HIV-1 long terminal repeat promoter region and their stabilization results in the inhibition of HIV-1 replication. Here, we identified helquat-based compounds as a new class of anti-HIV-1 inhibitors that inhibit HIV-1 replication at the stage of reverse transcription and provirus expression. Using Taq polymerase stop and FRET melting assays, we have demonstrated their ability to stabilize G-quadruplexes in the HIV-1 long-terminal repeat sequence. Moreover, these compounds were not binding to the general G-rich region, but rather to G-quadruplex-forming regions. Finally, docking and molecular dynamics calculations indicate that the structure of the helquat core greatly affects the binding mode to the individual G-quadruplexes. Our findings can provide useful information for the further rational design of inhibitors targeting G-quadruplexes in HIV-1.
Dengue virus (DENV) causes 390 million infections per year. Infections can be asymptomatic or range from mild fever to severe haemorrhagic fever and shock syndrome. Currently, no effective antivirals or safe universal vaccine is available. In the present work we tested different gold nanoparticles (AuNP) coated with ligands ω-terminated with sugars bearing multiple sulfonate groups. We aimed to identify compounds with antiviral properties due to irreversible (virucidal) rather than reversible (virustatic) inhibition. The ligands varied in length, in number of sulfonated groups as well as their spatial orientation induced by the sugar head groups. We identified two candidates, a glucose- and a lactose-based ligand showing a low EC50 (effective concentration that inhibit 50% of the viral activity) for DENV-2 inhibition, moderate toxicity and a virucidal effect in hepatocytes with titre reduction of Median Tissue Culture Infectious Dose log10TCID50 2.5 and 3.1. Molecular docking simulations complemented the experimental findings suggesting a molecular rationale behind the binding between sulfonated head groups and DENV-2 envelope protein.
- MeSH
- Antiviral Agents chemistry pharmacology MeSH
- Cell Line MeSH
- Hep G2 Cells MeSH
- Chlorocebus aethiops MeSH
- Dengue drug therapy MeSH
- Hepatocytes virology MeSH
- Metal Nanoparticles chemistry MeSH
- Humans MeSH
- Ligands MeSH
- Cell Line, Tumor MeSH
- Molecular Docking Simulation MeSH
- Vero Cells MeSH
- Dengue Virus drug effects MeSH
- Gold chemistry MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antiviral Agents MeSH
- Ligands MeSH
- Gold MeSH
HIV-1 protease (PR) is a homodimeric enzyme that is autocatalytically cleaved from the Gag-Pol precursor. Known PR inhibitors bind the mature enzyme several orders of magnitude more strongly than the PR precursor. Inhibition of PR at the precursor level, however, may stop the process at its rate-limiting step before the proteolytic cascade is initiated. Due to its structural heterogeneity, limited solubility and autoprocessing, the PR precursor is difficult to access by classical methods, and limited knowledge regarding precursor inhibition is available. Here, we describe a cell-based assay addressing precursor inhibition. We used a reporter molecule containing the transframe (TFP) and p6* peptides, PR, and N-terminal fragment of reverse transcriptase flanked by the fluorescent proteins mCherry and EGFP on its N- and C- termini, respectively. The level of FRET between EGFP and mCherry indicates the amount of unprocessed reporter, allowing specific monitoring of precursor inhibition. The inhibition can be quantified by flow cytometry. Additionally, two microscopy techniques confirmed that the reporter remains unprocessed within individual cells upon inhibition. We tested darunavir, atazanavir and nelfinavir and their combinations against wild-type PR. Shedding light on an inhibitor's ability to act on non-mature forms of PR may aid novel strategies for next-generation drug design.
- MeSH
- Atazanavir Sulfate pharmacology MeSH
- Cell Line MeSH
- Darunavir pharmacology MeSH
- Fluorescent Dyes MeSH
- HIV-1 enzymology MeSH
- HIV Protease Inhibitors pharmacology MeSH
- Anti-HIV Agents pharmacology MeSH
- Humans MeSH
- Nelfinavir pharmacology MeSH
- Protein Precursors antagonists & inhibitors MeSH
- Proteolysis MeSH
- Flow Cytometry MeSH
- Fluorescence Resonance Energy Transfer MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Atazanavir Sulfate MeSH
- Darunavir MeSH
- Fluorescent Dyes MeSH
- HIV Protease Inhibitors MeSH
- Anti-HIV Agents MeSH
- Nelfinavir MeSH
- Protein Precursors MeSH
