A5087884094- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Peptidase Inhibition and Analysis
- Mass Spectrometry Techniques and Applications
- Pharmacological Receptor Mechanisms and Effects
- Computational Drug Discovery Methods
- COVID-19 Clinical Research Studies
- interferon and immune responses
- Protease and Inhibitor Mechanisms
- Cytomegalovirus and herpesvirus research
- Viral Infections and Immunology Research
- Biochemical and Structural Characterization
- Respiratory viral infections research
- Advanced biosensing and bioanalysis techniques
- Synthesis and biological activity
- Biochemical and Molecular Research
- Cell death mechanisms and regulation
- Tea Polyphenols and Effects
- Monoclonal and Polyclonal Antibodies Research
- Advanced Proteomics Techniques and Applications
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
Johannes Gutenberg University Mainz
2020-2024
The University of Sydney
2013-2015
UNSW Sydney
2015
Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PL
Abstract The transmembrane serine protease 2 (TMPRSS2) primes the SARS-CoV-2 Spike (S) protein for host cell entry and represents a promising target COVID-19 therapy. Here we describe in silico development vitro characterization of peptidomimetic TMPRSS2 inhibitors. Molecular docking studies identified binders catalytic site, which were synthesized coupled to an electrophilic trap. compounds inhibit while demonstrating good off-target selectivity against selected coagulation proteases. Lead...
Trypsin-like serine proteases are involved in many important physiological processes like blood coagulation and remodeling of the extracellular matrix. On other hand, they also associated with pathological conditions. The urokinase-pwlasminogen activator (uPA), which is tissue remodeling, can increase metastatic behavior various cancer types when overexpressed dysregulated. Another member this protease class that received attention during SARS-CoV 2 pandemic TMPRSS2. It a transmembrane...
Covalent peptidomimetic protease inhibitors have gained a lot of attention in drug development recent years. They are designed to covalently bind the catalytically active amino acids through electrophilic groups called warheads. inhibition has an advantage terms pharmacodynamic properties but can also bear toxicity risks due non-selective off-target protein binding. Therefore, right combination reactive warhead with well-suited sequence is great importance. Herein, selectivities well-known...
The aim of this study was to investigate the transition from non-covalent reversible over covalent irreversible inhibition cysteine proteases by making delicate structural changes warhead scaffold. To end, dipeptidic rhodesain inhibitors with different
In many solid tumors, increased upregulation of transmembrane serine proteases (TTSPs) leads to an overactivation growth factors, which promotes tumor progression. Here, we have used a combinatorial methodology develop high-affinity tetrapeptidic inhibitors. A previous virtual screening 8000 peptide combinations against the crystal structure TTSP hepsin identified series recognition sequences, customized for non-prime substrate binding (P) sites this protease. combination top sequences with...
The increased resistance of circulating strains to current antiviral inhibitors the influenza virus necessitates that new antivirals and their mode action are identified. Influenza hemagglutinin is an ideal target given its function can block entry into host cells during early stages replication. This article describes molecular basis for inhibition H1 H5 by entry-blocker peptide using companion docking mass spectrometry-based experiments.A combination hemagglutination assays, computational...
Fluorometric assays are one of the most frequently used methods in medicinal chemistry. Over last 50 years, reporter molecules for detection protease activity have evolved from first-generation colorimetric p-nitroanilides, through FRET substrates, and 7-amino-4-methyl coumarin (AMC)-based substrates. The aim further substrate development is to increase sensitivity reduce vulnerability assay interferences. Herein, we describe a new generation substrates based on...