The coronavirus disease 2019 pandemic accelerated drug/vaccine development processes, integrating scientists all over the globe to create therapeutic alternatives against this virus. In this work, we have collected information regarding proteins from SARS-CoV-2 and humans and how these proteins interact. We have also collected information from public databases on protein–drug interactions. We represent this data as networks that allow us to gain insights into protein–protein interactions between both organisms. With the collected data, we have obtained statistical metrics of the networks. This data analysis has allowed us to find relevant information on which proteins and drugs are the most relevant from the network pharmacology perspective. This method not only allows us to focus on viral proteins as the main targets for COVID-19 but also reveals that some human proteins could be also important in drug repurposing campaigns. As a result of the analysis of the SARS-CoV-2–human interactome, we have identified some old drugs, such as disulfiram, auranofin, gefitinib, suloctidil, and bromhexine as potential therapies for the treatment of COVID-19 deciphering their potential complex mechanism of action.
Neurodegenerative diseases (NDD) have been of great interest to scientists for a long time due to their multifactorial character. Among these pathologies, Alzheimer’s disease (AD) is of special relevance, and despite the existence of approved drugs for its treatment, there is still no efficient pharmacological therapy to stop, slow, or repair neurodegeneration. Existing drugs have certain disadvantages, such as lack of efficacy and side effects. Therefore, there is a real need to discover new drugs that can deal with this problem. However, as AD is multifactorial in nature with so many physiological pathways involved, the most effective approach to modulate more than one of them in a relevant manner and without undesirable consequences is through polypharmacology. In this field, there has been significant progress in recent years in terms of pharmacoinformatics tools that allow the discovery of bioactive molecules with polypharmacological profiles without the need to spend a long time and excessive resources on complex experimental designs, making the drug design and development pipeline more efficient. In this review, we present from different perspectives how pharmacoinformatics tools can be useful when drug design programs are designed to tackle complex diseases such as AD, highlighting essential concepts, showing the relevance of artificial intelligence and new trends, as well as different databases and software with their main results, emphasizing the importance of coupling wet and dry approaches in drug design and development processes.
Astrocytes are critical for the metabolic, structural and functional modulatory support of the brain. Lipotoxicity or high levels of saturated fatty acid as Palmitate (PA) has been associated with neurotoxicity, the loss or change of astrocytic functionality, and the etiology and progression of neurodegenerative diseases such as Parkinson or Alzheimer. Several molecular mechanisms of PA’s effect in astrocytes have been described, yet the role of epigenetic regulation and chromatin architecture have not been fully explored. In this study, we developed a multi-omic epigenetic-based model to identify the molecular mechanisms of lipotoxic PA activity in astrocytes. We used data from nine histone modifications, location of Topological Associated Domains (TADs) and transcriptional CTCF regions, where we identified the basal astrocyte epigenetic landscape. Moreover, we integrated transcriptomic data of astrocytic cellular response to PA with the epigenetic multi-omic model to identify lipotoxic-induced molecular mechanisms. The multi-omic model showed that chromatin conformation in astrocytes treated with PA have response genes located within shared topological domains, in which most of them also showed either repressive or enhancing marks in the Chip-Seq enrichment, reinforcing the idea that epigenetic regulation has a huge impact on the lipotoxic mechanisms of PA in the brain.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.