A5077818356- SARS-CoV-2 and COVID-19 Research
- Galectins and Cancer Biology
- Toxin Mechanisms and Immunotoxins
- Cancer Mechanisms and Therapy
- Endoplasmic Reticulum Stress and Disease
- Multiple Sclerosis Research Studies
- Rabies epidemiology and control
- Nitric Oxide and Endothelin Effects
- Poxvirus research and outbreaks
- Reproductive System and Pregnancy
- vaccines and immunoinformatics approaches
- Organoselenium and organotellurium chemistry
- Cancer-related Molecular Pathways
- Inflammasome and immune disorders
- Cancer, Hypoxia, and Metabolism
- Herpesvirus Infections and Treatments
- Cancer, Lipids, and Metabolism
- Peptidase Inhibition and Analysis
- Phosphodiesterase function and regulation
- Protein Kinase Regulation and GTPase Signaling
- Metabolism, Diabetes, and Cancer
University of Alberta
2023-2024
The main protease of SARS-CoV-2 (Mpro) is the most promising drug target against coronaviruses due to its essential role in virus replication. With newly emerging variants there a concern that mutations Mpro may alter structural and functional properties subsequently potency existing potential antivirals. We explored effect 31 belonging 5 (VOCs) on catalytic parameters substrate specificity, which revealed changes binding rate cleavage viral peptide. Crystal structures 11 mutants provided...
Monkeypox virus (MPXV) infections in humans cause neurological disorders while studies of MPXV-infected animals indicate that the penetrates brain. Pyroptosis is an inflammatory type regulated cell death, resulting from plasma membrane rupture (PMR) due to oligomerization cleaved gasdermins pore formation. Herein, we investigated human neural tropism MPXV compared another orthopoxvirus, vaccinia (VACV), as well its effects on immune responses and death. Astrocytes were most permissive (and...
The recent emergence of SARS-CoV-2 in the human population has caused a global pandemic. virus encodes two proteases, M
Abstract Background In humans, two ubiquitously expressed N-myristoyltransferases, NMT1 and NMT2, catalyze myristate transfer to proteins facilitate membrane targeting signaling. We investigated the expression of NMT s in numerous cancers found that NMT2 levels are dysregulated by epigenetic suppression, particularly so hematologic malignancies. This suggests pharmacological inhibition remaining could allow for selective killing these cells, sparing normal cells with both NMTs. Methods...
Abstract Introduction. Zelenirstat (PCLX-001) is a small molecule inhibitor of N-myristoylation, process that involves addition the fatty acid myristate to over 200 proteins by two N-myristoyltransferases (NMT1 and 2). These include Src family kinases c-Abl. Inhibition N-myristoylation zelenirstat leads degradation non-myristoylated cancer cell death. We conducted phase I trial evaluate safety, tolerability, maximally tolerated dose (MTD) in patients with refractory cancer. Methods....
ABSTRACT Main protease of SARS-CoV-2 (M pro ) is the most promising drug target against coronaviruses due to its essential role in virus replication. With newly emerging variants there a concern that mutations M may alter structural and functional properties subsequently potency existing potential antivirals. We explored effect 31 belonging 5 (VOC) on catalytic parameters substrate specificity, which revealed changes binding rate cleavage viral peptide. Crystal structures 11 mutants provided...
Abstract PCLX-001 is a first-in-kind drug that targets protein modification essential for membrane anchorage and signalling, has been under human clinical trial evaluation the treatment of lymphoma solid malignancies over year. In human, 600 proteoforms are modified with fatty acid myristate by two N-myristoyltransferases: NMT1 NMT2. These include many proto-oncogenic proteins (e.g. Src-family kinases c-Abl) metabolic regulators AMPK β subunit). Thus, we validated potential NMTs as oncology...