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Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance.
Viruses
January 2025
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
The ongoing monkeypox (mpox) disease outbreak has spread to multiple countries in Central Africa and evidence indicates it is driven by a more virulent clade I monkeypox virus (MPXV) strain than the clade II strain associated with the 2022 global mpox outbreak, which led the WHO to declare this mpox outbreak a public health emergency of international concern. The FDA-approved small molecule antiviral tecovirimat (TPOXX) is recommended to treat mpox cases with severe symptoms, but the limited efficacy of TPOXX and the emergence of TPOXX resistant MPXV variants has challenged this medical practice of care and highlighted the urgent need for alternative therapeutic strategies. In this study we have used vaccinia virus (VACV) as a surrogate of MPXV to assess the antiviral efficacy of combination therapy of TPOXX together with mycophenolate mofetil (MMF), an FDA-approved immunosuppressive agent that we have shown to inhibit VACV and MPXV, or the N-myristoyltransferase (NMT) inhibitor IMP-1088.
View Article and Find Full Text PDFTargeting Bacterial Cell Division with Benzodioxane-Benzamide FtsZ Inhibitors as a Novel Strategy to Fight Gram-Positive Ovococcal Pathogens.
Int J Mol Sci
January 2025
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Luigi Mangiagalli, 25, 20133 Milan, Italy.
The widespread emergence of antimicrobial resistance (AMR) is a serious threat to global public health and among Gram-positive cocci, constitutes a priority in the list of AMR-threatening pathogens. To counteract this fundamental problem, the bacterial cell division cycle and the crucial proteins involved in this process emerged as novel attractive targets. FtsZ is an essential cell division protein, and FtsZ inhibitors, especially the benzamide derivatives, have been exploited in the last decade.
View Article and Find Full Text PDFA novel peptide encoded by circSRCAP confers resistance to enzalutamide by inhibiting the ubiquitin-dependent degradation of AR-V7 in castration-resistant prostate cancer.
J Transl Med
January 2025
Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China.
Background: The sustained activation of androgen receptor splice variant-7 (AR-V7) is a key factor in the resistance of castration-resistant prostate cancer (CRPC) to second-generation anti-androgens such as enzalutamide (ENZ). The AR/AR-V7 protein is regulated by the E3 ubiquitin ligase STUB1 and a complex involving HSP70, but the precise mechanism remains unclear.
Methods: High-throughput RNA sequencing was used to identify differentially expressed circular RNAs (circRNAs) in ENZ-resistant and control CRPC cells.
Optimizing Thermal Stability: Evaluating the Impact of Heterofunctional Hydrophobic Supports on Immobilized Flaxseed Lipase.
Appl Biochem Biotechnol
January 2025
Department of Food Engineering, State University of Maringá, Maringá, PR, Brazil.
Lipases have catalytic capacity in various processes such as hydrolysis. Those derived from plant sources, such as linseed, offer an economical alternative. The immobilization process facilitates the recovery and reuse of lipase, providing advantages such as resistance to high temperatures and difficulties in recovering and reusing free lipases, which makes product separation difficult.
View Article and Find Full Text PDFExploring a metal/base-free porphyrin involving a carboxyl-functionalized pyridine moiety for photocatalytic -arylation of benzamide validated using RSM.
Org Biomol Chem
January 2025
Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore, Tamil Nadu-632014, India.
A porphyrin comprising a carboxyl-functionalized pyridine moiety was synthesized and characterized using H NMR, C NMR, FT-IR, powder-XRD, BET, ICP-MS, SEM and EDAX. The proton level (H = 1.19) and energy band gap (1.
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