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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 PDFSex-specific impact of obstructive sleep apnea on peripheral blood mononuclear cells.
Sleep Breath
December 2024
Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, 55901, USA.
Purpose: Experimental sleep disruption in healthy adults is more deleterious to immune function in females relative to males; however, it remains unknown if this translates to patients with obstructive sleep apnea (OSA). Thus, this study explored sex differences in peripheral blood mononuclear cells (PBMCs) from patients with untreated OSA.
Methods: Participants completed sleep studies to identify the presence of OSA via the apnea-hypopnea index (AHI).
Sample Preparation for Global Metabolic Profiling of Vaccinia Virus-Infected Primary Human Foreskin Fibroblasts.
Methods Mol Biol
December 2024
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, USA.
Vaccinia virus (VACV), the prototype member of the Poxviridae family, has played a crucial role in medicine as a key component in the development of smallpox vaccines, contributing to the eradication of this deadly disease. Beyond its historical significance, VACV continues to be pivotal in researching metabolic alterations induced by viral infections. Studies have revealed that VACV can impact pathways such as glycolysis, the tricarboxylic acid (TCA) cycle, and lipid metabolism in host cells, offering valuable insights into host-virus interactions and broader cellular metabolism.
View Article and Find Full Text PDFAn Evolutionary Framework Exploiting Virologs and Their Host Origins to Inform Poxvirus Protein Functions.
Methods Mol Biol
December 2024
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Poxviruses represent evolutionary successful infectious agents. As a family, poxviruses can infect a wide variety of species including humans, fish, and insects. While many other viruses are species-specific, an individual poxvirus species is often capable of infecting diverse hosts and cell types.
View Article and Find Full Text PDFHigh-Throughput Single-Cell Analysis of Vaccinia Virus Infection.
Methods Mol Biol
December 2024
School of Life and Environmental Science, The University of Sydney, Camperdown, NSW, Australia.
Here, we describe a robust and flexible method for analyzing the infection of single cells with a fluorescent-reporter virus, with real-time tracking of infected cells through microscopy. We subsequently generate quantitative data from the resulting time-lapse microscopy, and harness these data to generate biologically meaningful parameters at scale. Our methodology offers a practical solution for researchers seeking to understand the complexities and variability of virus-host interactions at a granular level.
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