The current outbreak of mpox presents a significant threat to the global community. However, the lack of mpox-specific drugs necessitates the identification of additional candidates for clinical trials. In this study, a network medicine framework was used to investigate poxviruses-human interactions to identify potential drugs effective against the mpox virus (MPXV). The results indicated that poxviruses preferentially target hubs on the human interactome, and that these virally-targeted proteins (VTPs) tend to aggregate together within specific modules. Comorbidity analysis revealed that mpox is closely related to immune system diseases. Based on predicted drug-target interactions, 268 drugs were identified using the network proximity approach, among which 23 drugs displaying the least side-effects and significant proximity to MPXV were selected as the final candidates. Lastly, specific drugs were explored based on VTPs, differentially expressed proteins, and intermediate nodes, corresponding to different categories. These findings provide novel insights that can contribute to a deeper understanding of the pathogenesis of MPXV and development of ready-to-use treatment strategies based on drug repurposing.
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http://dx.doi.org/10.1016/j.ijbiomac.2024.132468 | DOI Listing |
PLoS One
January 2025
Center of Medical and Bio-Allied Health Sciences Research (CMBHSR), Ajman University, Ajman, United Arab Emirates.
Epigenetic processes are the critical events in carcinogenesis. Histone modification plays a crucial role in gene expression regulation, where histone deacetylases (HDACs) are key players in epigenetic processes. Inhibiting HDACs has shown promise in modern cancer therapy.
View Article and Find Full Text PDFBackground: The limited treatment options for Alzheimer's emphasizes the need to explore novel drug targets and bring new therapeutics to market. Drug repurposing is an efficient route to bring a safe and effective treatment to the clinic. Agomelatine (AGO) was identified by a high-throughput drug screening algorithm as having mechanistic potential to treat Alzheimer's.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Karolinska Institutet, Solna, Sweden.
Background: High age is the biggest risk factor for Alzheimer's disease (AD). Approved drugs that slow down the aging process have the potential to be repurposed for the primary prevention of AD. The aim of our project was to use a reverse translational approach to identify such drug candidates in epidemiological data followed by validation in cell-based models and animal models of aging and AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Cleveland Clinic, Cleveland, OH, USA.
Background: Microglia have been implicated as a key aspect of the pathology of Alzheimer's disease (AD). However, high microglial heterogeneities, including disease-associated microglia (DAM), tau microglia (tau-pathology related), and neuroinflammation-like microglia (NIM), hinder the development of microglia-targeted treatment.
Method: In this study, we integrated ∼0.
Alzheimers Dement
December 2024
Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany, Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
Background: Despite recent breakthroughs, Alzheimer's disease (AD) remains untreatable. In addition, we are still lacking robust biomarkers for early diagnosis and promising novel targets for therapeutic intervention. To enable utilizing the entirety of molecular evidence in the discovery and prioritization of potential novel biomarkers and targets, we have developed the AD Atlas, a network-based multi-omics data integration platform.
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