A5044440190- RNA and protein synthesis mechanisms
- SARS-CoV-2 and COVID-19 Research
- Computational Drug Discovery Methods
- X-ray Diffraction in Crystallography
- Click Chemistry and Applications
- Crystallization and Solubility Studies
- Ubiquitin and proteasome pathways
- Innovative Microfluidic and Catalytic Techniques Innovation
- Chemical Synthesis and Analysis
- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
Newcastle University
2020-2022
Cancer Research UK
2020-2022
Abstract COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no antiviral drugs or vaccines were developed against the closely related coronavirus, SARS-CoV-1 MERS-CoV, despite previous zoonotic outbreaks. To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through combined mass spectrometry X-ray approach SARS-CoV-2 main protease, one two cysteine viral proteases essential replication. Our...
Summary COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no antiviral drugs or vaccines were developed against the closely related coronavirus, SARS-CoV-1 MERS-CoV, despite previous zoonotic outbreaks. To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through combined mass spectrometry X-ray approach SARS-CoV-2 main protease, one two cysteine viral proteases essential replication. Our...
The development of ligands for biological targets is critically dependent on the identification sites proteins that bind molecules with high affinity. A set compounds, called FragLites, can identify such sites, along interactions required to gain affinity, by X-ray crystallography. We demonstrate utility FragLites in mapping binding bromodomain BRD4 and ATAD2 FragLite comparable a full fragment screen identifying ligand key interactions. extend analogous compounds derived from amino acids...
High-throughput screening provides one of the most common ways finding hit compounds. Lead-like libraries, in particular, provide hits with compatible functional groups and vectors for structural elaboration physical properties suitable optimization. Library synthesis approaches can lead to a lack chemical diversity because they employ parallel derivatization building blocks using single reaction types. We address this problem through "build-couple-transform" paradigm generation lead-like...