ArticleToxicology and applied pharmacology2020
Safety assessment of drug combinations used in COVID-19 treatment: in silico toxicogenomic data-mining approach.
Article in Toxicology and applied pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Editorial: Phytochemicals in modern medicine: health benefits and toxicological considerations.Frontiers in medicine · 2026Article
- A review of the scientific literature on experimental toxicity studies of COVID-19 vaccines, with special attention to publications in toxicology journals.Archives of toxicology · 2024Review
- Identification of potential biomarkers for cerebral palsy and the development of prediction models.Experimental biology and medicine (Maywood, N.J.) · 2024Article
- Article
- Prioritizing and queueing the emergency departments' patients using a novel data-driven decision-making methodology, a real case study.Expert systems with applications · 2022Article
- Identifying Drug-Induced Liver Injury Associated With Inflammation-Drug and Drug-Drug Interactions in Pharmacologic Treatments for COVID-19 by Bioinformatics and System Biology Analyses: The Role of Pregnane X Receptor.Frontiers in pharmacology · 2022Article
- Network-Based Analysis Reveals Novel Biomarkers in Peripheral Blood of Patients With Preeclampsia.Frontiers in molecular biosciences · 2022Article
- In silico functional and pathway analysis of risk genes and SNPs for type 2 diabetes in Asian population.PloS one · 2022Article
- Construction of an autophagy interaction network based on competitive endogenous RNA reveals the key pathways and central genes of SARS-CoV-2 infection in vivo.Microbial pathogenesis · 2021Article
- An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease.Molecular informatics · 2021Article
- Predictive association ofPharmacogenomics · 2021Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Improvement of COVID-19 clinical condition was seen in studies where combination of antiretroviral drugs, lopinavir and ritonavir, as well as immunomodulant antimalaric, chloroquine/hydroxychloroquine together with the macrolide-type antibiotic, azithromycin, was used for patient's treatment. Although these drugs are "old", their pharmacological and toxicological profile in SARS-CoV-2 - infected patients are still unknown. Thus, by using in silico toxicogenomic data-mining approach, we aimed to assess both risks and benefits of the COVID-19 treatment with the most promising candidate drugs combinations: lopinavir/ritonavir and chloroquine/hydroxychloroquine + azithromycin. The Comparative Toxicogenomics Database (CTD; http://CTD.mdibl.org), Cytoscape software (https://cytoscape.org) and ToppGene Suite portal (https://toppgene.cchmc.org) served as a foundation in our research. Our results have demonstrated that lopinavir/ritonavir increased the expression of the genes involved in immune response and lipid metabolism (IL6, ICAM1, CCL2, TNF, APOA1, etc.). Chloroquine/hydroxychloroquine + azithromycin interacted with 6 genes (CCL2, CTSB, CXCL8, IL1B, IL6 and TNF), whereas chloroquine and azithromycin affected two additional genes (BCL2L1 and CYP3A4), which might be a reason behind a greater number of consequential diseases. In contrast to lopinavir/ritonavir, chloroquine/hydroxychloroquine + azithromycin downregulated the expression of TNF and IL6. As expected, inflammation, cardiotoxicity, and dyslipidaemias were revealed as the main risks of lopinavir/ritonavir treatment, while chloroquine/hydroxychloroquine + azithromycin therapy was additionally linked to gastrointestinal and skin diseases. According to our results, these drug combinations should be administrated with caution to patients suffering from cardiovascular problems, autoimmune diseases, or acquired and hereditary lipid disorders.
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