A5072676788- Influenza Virus Research Studies
- RNA and protein synthesis mechanisms
- Microbial Natural Products and Biosynthesis
- HIV/AIDS drug development and treatment
- DNA and Nucleic Acid Chemistry
- Bioactive Compounds and Antitumor Agents
- Protein Structure and Dynamics
- Toxin Mechanisms and Immunotoxins
- Various Chemistry Research Topics
- Synthesis and biological activity
- Pharmacological Effects of Natural Compounds
- Flavonoids in Medical Research
- interferon and immune responses
- Environmental Science and Water Management
- Molecular spectroscopy and chirality
- Advanced biosensing and bioanalysis techniques
- Monoclonal and Polyclonal Antibodies Research
- Medicinal Plants and Bioactive Compounds
- Cancer therapeutics and mechanisms
- Computational Drug Discovery Methods
- DNA Repair Mechanisms
- Nutrition, Genetics, and Disease
- Viral Infections and Immunology Research
- HIV Research and Treatment
- Tuberculosis Research and Epidemiology
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2020-2025
Charles University
2020-2023
Czech Academy of Sciences
2023
Influenza virus, an RNA virus of the Orthomyxoviridae family, is responsible for widespread seasonal epidemics that result in 3 to 5 million severe illnesses and more than half a million...
The biological effects of flavonoids on mammal cells are diverse, ranging from scavenging free radicals and anti-cancer activity to anti-influenza activity. Despite appreciable effort understand the flavonoids, there is no clear consensus about their precise mode-of-action at a cellular level. Here, we report development validation screening assay based AlphaScreen technology illustrate its application for determination inhibitory potency large set polyols against PA N-terminal domain...
Influenza A virus (IAV) encodes a polymerase composed of three subunits: PA, with endonuclease activity, PB1 activity and PB2 host RNA five-prime cap binding site. Their cooperation stepwise activation include process called cap-snatching, which is crucial step in the IAV life cycle. Reproduction can be blocked by disrupting interaction between domain cap. An inhibitor this pimodivir (VX-787) recently entered third phase clinical trial; however, several mutations that cause resistance to...
The part of the influenza polymerase PA subunit featuring endonuclease activity is a target for anti-influenza therapies, including FDA-approved drug Xofluza. A general feature inhibitors their ability to chelate Mg2+ or Mn2+ ions located in enzyme’s catalytic site. Previously, we screened panel flavonoids inhibition and found luteolin its C-glucoside orientin be potent inhibitors. Through structural analysis, identified presence 3′,4′-dihydroxyphenyl moiety as crucial sub-micromolar...
Influenza viruses can cause severe respiratory infections in humans, leading to nearly half a million deaths worldwide each year. Improved antiviral drugs are needed address the threat of development novel pandemic strains. Current therapeutic interventions target three key proteins viral life cycle: neuraminidase, M2 channel and RNA-dependent-RNA polymerase. Protein-protein interactions between influenza polymerase subunits potential new targets for drug development. Using newly developed...
The influenza RNA-dependent RNA polymerase harbours an endonuclease subunit characterized by a catalytic site housing two divalent metal ions. By effectively chelating both Mg
Influenza RNA-dependent RNA polymerase (RdRp) is a heterotrimeric complex composed of the acidic (PA), basic 1 (PB1), and 2 (PB2) subunits.The RdRp has an essential role in life cycle virus as it responsible for viral replication transcription.Two subunits, PA PB1 share extensive interface.However, their assembly depends on relatively small hydrophobic cleft formed by C-terminus (CPA) (Fig. 1A).The N-terminus binds to CPA form 310 helix [1,2].Disrupting such important protein-protein...