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Dengue virus is particularly sensitive to interference with long-chain fatty acid elongation and desaturation.
J Biol Chem
January 2025
Institute of Virology, Philipps University Marburg, Marburg, Germany. Electronic address:
Orthoflaviviruses are emerging arthropod-borne pathogens whose replication cycle is tightly linked to host lipid metabolism. Previous lipidomic studies demonstrated that infection with the closely related hepatitis C virus (HCV) changes the fatty acid (FA) profile of several lipid classes. Lipids in HCV-infected cells had more very long-chain and desaturated FAs and viral replication relied on functional FA elongation and desaturation.
View Article and Find Full Text PDFNovel isoxazole thiophene-containing compounds active against Mycobacterium tuberculosis.
Bioorg Med Chem Lett
January 2025
Calibr-Skaggs Institute for Innovative Medicines, a division of Scripps Research, La Jolla, CA 92037, United States. Electronic address:
Screening of the ChemDiv molecular library in cholesterol media against Mycobacterium tuberculosis (Mtb) H37Rv strain identified a novel isoxazole thiophene hit as a putative Rv1625c/Cya activator with a promising in vitro activity and good pharmacokinetic properties. Twenty-nine analogs were synthesized to assess the structure-activity relationships (SAR) to further improve potency. The most notable analog was P15, which showed an intramacrophage EC = 1.
View Article and Find Full Text PDFTuberculosis and people who use drugs: why focus on this overlooked population is important and why adapted interventions are necessary.
Lancet Glob Health
January 2025
Pathogenesis and Control of Chronic and Emerging Infections, University of Montpellier, Institut National de la Santé et de la Recherche Médicale, Montpellier, France. Electronic address:
People who use drugs show a higher incidence and prevalence of tuberculosis than people who do not use drugs in areas where Mycobacterium tuberculosis is endemic. However, this population is largely neglected in national tuberculosis programmes. Strategies for active case finding, screening, and linkage to care designed for the general population are not adapted to the needs of people who use drugs, who are stigmatised and difficult to reach.
View Article and Find Full Text PDFWhole genome sequencing characterization of Clostridioides difficile from Bulgaria during the COVID-19 pandemic.
Diagn Microbiol Infect Dis
January 2025
National Reference Laboratory of Control and Monitoring of Antibiotic Resistance (NRL-CMAR), Department Microbiology, National Center of Infectious and Parasitic Diseases (NCIPD), 26 Yanko Sakazov Blvd., Sofia, Bulgaria.
Increased incidence of Clostridioides difficile infections were documented in Bulgarian hospitals during COVID-19. WGS was performed on 39 isolates from seven hospitals during 2015-2022. Antimicrobial resistance and toxin genes were inferred from genomes.
View Article and Find Full Text PDFInhibitors of NADH-O-methylquinone compound a class of antitubercular drugs.
Mol Divers
January 2025
Department of Laboratory Medicine, The Fourth People's Hospital of Nanhai District of Foshan City, Foshan, 528000, Guangdong, China.
Disruption of the mycobacterial redox homeostasis leads to irreversible stress induction and cell death. Hydroquinone scaffolds, as a new type of redox cycling anti-tuberculosis chemotypes, exhibit potent bactericidal activity against non-replicating, nutrient-deprived phenotypically drug-resistant bacteria. Evidences from microbiological, biochemical, and genetic studies indicate that the redox-driven mode of action relies on the reduction of quinones by type II NADH dehydrogenase (NDH2), generating reactive oxygen species (ROS) of bactericidal level.
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