Publications by authors named "S Lovell"
Acetyl CoA synthetases (ACS) have emerged as drug targets for the treatment of cancer, metabolic diseases as well as fungal and parasitic infections. Although a variety of small molecule ACS inhibitors have been discovered, the systematic optimization of these molecules has been slowed by a lack of structural information regarding their mechanism of inhibition. Through a chemical genetic-based, synthetic lethal screen of the human fungal pathogen , we identified an isoxazole-based ACS inhibitor with antifungal activity and exquisite selectivity for the Acs1 relative to human ACSS2 as well as other fungal ACSs.
View Article and Find Full Text PDFStructures of Trichomonas vaginalis macrophage migratory inhibitory factor.
Acta Crystallogr F Struct Biol Commun
December 2024
Article Synopsis
- Trichomonas vaginalis is a one-celled parasite that causes trichomoniasis, the most common nonviral STD worldwide, and it uses mimicry of human proteins to evade the immune system.
- The parasite produces a protein called TvMIF, which helps it survive stress, boosts prostate cell growth, and triggers inflammation, paralleling the effects of human MIF.
- Recent studies have revealed the structure of TvMIF, showing it has a similar shape to human versions, suggesting that understanding this protein can aid in developing new drugs.
Article Synopsis
- * The study introduces a novel counter-selection method using phage display to identify covalent macrocyclic ligands that can disrupt protein-protein interactions, specifically targeting the SARS-CoV-2 Spike-ACE2 interaction.
- * The identified covalent inhibitors showed strong antiviral effects, demonstrating their permanence due to the covalent binding mechanism, highlighting the potential for developing long-lasting drugs that interfere with critical protein interactions.
Crystal structure of N-terminally hexahistidine-tagged Onchocerca volvulus macrophage migration inhibitory factor-1.
Acta Crystallogr F Struct Biol Commun
December 2024
Article Synopsis
- Onchocerca volvulus is responsible for serious health issues, including blindness and neurological diseases, and current treatments like ivermectin can't be safely used in pregnant women or those co-infected with Loa loa.
- Researchers at the Seattle Structural Genomics Center for Infectious Disease have successfully produced and crystallized a potential drug target called OvMIF-1, which has a unique jellyfish-like structure.
- The study suggests that deleting its N-terminal tag could reveal a larger cavity for drug targeting, indicating the need for further analysis to confirm the true biological structure of OvMIF-1.
Nontuberculous mycobacteria (NTM) are emerging human pathogens linked to severe pulmonary diseases. Current treatments involve the prolonged use of multiple drugs and are often ineffective. Bacterial dihydrofolate reductase (DHFR) is a key enzyme targeted by antibiotics in Gram-negative bacterial infections.
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