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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 PDFNew Treatment Regimens, New Drugs, and New Treatment Goals for Lupus Nephritis.
J Clin Med
January 2025
Nephrology and Dialysis Unit, Meyer Children's Hospital IRCCS, 50139 Florence, Italy.
Lupus nephritis is one of the most severe manifestations of systemic lupus erythematosus, affecting roughly 40% of all lupus patients. With the introduction of cyclophosphamide and mycophenolate mofetil, outcomes have dramatically improved. However, 10% of patients still progress towards end-stage kidney disease, which carries an elevated mortality rate.
View Article and Find Full Text PDFThe Ca-actin-cytoskeleton axis in podocytes is an important, non-immunologic target of immunosuppressive therapy in proteinuric kidney diseases.
Pediatr Nephrol
January 2025
Department of Pediatrics, University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Street 62, 50937, Cologne, Germany.
The integrity of the filtration barrier of the kidney relies on the proper composition of podocyte interdigitating foot processes. Their architecture is supported by a complex actin-cytoskeleton. Following podocyte stress or injury, podocytes encounter structural changes, including rearrangement of the actin network and subsequent effacement of the foot processes.
View Article and Find Full Text PDFCan you have a cake and eat it? Comparing reducing mycophenolate versus switching to everolimus for kidney transplants with new-onset BKPyV-DNAemia.
Kidney Int
February 2025
Transplantation & Clinical Virology, Department of Biomedicine, University of Basel, Basel Switzerland. Electronic address:
BK polyomavirus remains a vexing issue in kidney transplantation. There are no antiviral drugs, and solely reducing immunosuppression is recommended for management. However, evidence from randomized controlled studies lacks defining clearance of BK polyomavirus-DNAemia and/or nephropathy as a primary outcome.
View Article and Find Full Text PDFMycophenolate mofetil: an update on its mechanism of action and effect on lymphoid tissue.
Front Immunol
January 2025
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
Introduction: Mycophenolate mofetil (MMF) is an immunosuppressive drug administered in the management of both autoimmune diseases and organ transplantation. The main aims of the study were: (a) to obtain information regarding the safety of using MMF in respect of its effect on normal T and B cells in lymphoid tissues; (b) to investigate whether the generation of inducible Foxp3-expressing regulatory T cells (Treg) might constitute additional mechanisms underlying the immunosuppressive properties of MMF.
Methods: The effect of MMF ( studies) and its active metabolite, mycophenolic acid, ( studies) on murine CD4 and CD8 T cells as well as B cells was determined, regarding: (a) absolute count, proliferation and apoptosis of these cells ( studies); (b) absolute count of these cells in the head and neck lymph nodes, mesenteric lymph nodes and the spleen ( studies).
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