DCcov: Repositioning of drugs and drug combinations for SARS-CoV-2 infected lung through constraint-based modeling

Kishk, Ali; Pacheco, Maria Pires; Sauter, Thomas

doi:10.1016/j.isci.2021.103331

Cited by 20 publications

(21 citation statements)

References 94 publications

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“…For example, Kishk et al. found ferroptosis as a candidate prognostic and target pathway for COVID-19 ( 14 ); Luo et al. discovered that ferroptosis impacts tumor immunity and it can help to improve the efficacy of patients’ immunotherapy ( 15 ); Zhao et al.…”

Section: Introductionmentioning

confidence: 99%

FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations

Zhou

Yuan

et al. 2022

Nucleic Acids Research

142

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Ferroptosis is a mode of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation. It is closely linked to the pathophysiological processes in many diseases. Since our publication of the first ferroptosis database in 2020 (FerrDb V1), many new findings have been published. To keep up with the rapid progress in ferroptosis research and to provide timely and high-quality data, here we present the successor, FerrDb V2. It contains 1001 ferroptosis regulators and 143 ferroptosis-disease associations manually curated from 3288 articles. Specifically, there are 621 gene regulators, of which 264 are drivers, 238 are suppressors, 9 are markers, and 110 are unclassified genes; and there are 380 substance regulators, with 201 inducers and 179 inhibitors. Compared to FerrDb V1, curated articles increase by >300%, ferroptosis regulators increase by 175%, and ferroptosis-disease associations increase by 50.5%. Circular RNA and pseudogene are novel regulators in FerrDb V2, and the percentage of non-coding RNA increases from 7.3% to 13.6%. External gene-related data were integrated, enabling thought-provoking and gene-oriented analysis in FerrDb V2. In conclusion, FerrDb V2 will help to acquire deeper insights into ferroptosis. FerrDb V2 is freely accessible at http://www.zhounan.org/ferrdb/.

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Section: Introductionmentioning

confidence: 99%

FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations

Zhou

Yuan

et al. 2022

Nucleic Acids Research

142

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“…The latter have employed different types of experimental data, such as data obtained from different cell lines (e.g., see [ 74 ]), patient samples (e.g., see [ 108 ]), or a combinations of both (e.g., [ 102 ]). Most of the approaches devoted to the GEM-based analysis of COVID-19 focused on the identification of enriched metabolic reactions and pathways (e.g., see [ 102 , 106 , 107 ]) and/or to the identification of potential antiviral targets (e.g., see [ 98 , 99 , 105 ]) and drug repurposing (e.g., see [ 100 , 103 ]). Reported studies also focused on the identification of metabolic reactions guiding disease severity [ 108 ], and on the analysis of cancer metabolism affected by SARS-CoV-2 infection [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

“…Kishk et al proposed another pipeline for GEM-based drug repurposing using FBA [ 103 ]. As in most other works, the generic models (Recon 2 [ 20 ] and Recon3D [ 21 ]) were extended with a VBOF according to [ 98 ].…”

Section: Covid-19 Applications Of Context-specific Genome-scale Metab...mentioning

confidence: 99%

Context-Specific Genome-Scale Metabolic Modelling and Its Application to the Analysis of COVID-19 Metabolic Signatures

Moškon

Režen

2023

Metabolites

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Genome-scale metabolic models (GEMs) have found numerous applications in different domains, ranging from biotechnology to systems medicine. Herein, we overview the most popular algorithms for the automated reconstruction of context-specific GEMs using high-throughput experimental data. Moreover, we describe different datasets applied in the process, and protocols that can be used to further automate the model reconstruction and validation. Finally, we describe recent COVID-19 applications of context-specific GEMs, focusing on the analysis of metabolic implications, identification of biomarkers and potential drug targets.

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“…The results of these studies led the authors to elaborate on the possibilities of a few re-purposed antiferroptosis drugs for the therapy of this infection. 348 Cell membrane altered polarization and the overload of cations can also affect blood coagulation, endothelial and neural functionality; more generally the electro-chemical events occurring at the cell wall significantly impact the metabolic pathways of a number of organs.…”

Section: Discussionmentioning

confidence: 99%

COVID-19, Cation Dysmetabolism, Sialic Acid, CD147, ACE2, Viroporins, Hepcidin and Ferroptosis: A Possible Unifying Hypothesis

Cavezzi

Menicagli

Troiani³

et al. 2022

F1000Res

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Background: iron and calcium dysmetabolism, with hyperferritinemia, hypoferremia, hypocalcemia and anemia have been documented in the majority of COVID-19 patients at later/worse stages. Furthermore, complementary to ACE2, both sialic acid (SA) molecules and CD147 proved relevant host receptors for SARS-CoV-2 entry, which explains the viral attack to multiple types of cells, including erythrocytes, endothelium and neural tissue. Several authors advocated that cell ferroptosis may be the core and final cell degenerative mechanism. Methods: a literature research was performed in several scientific search engines, such as PubMed Central, Cochrane Library, Chemical Abstract Service. More than 500 articles were retrieved until mid-December 2021, to highlight the available evidence about the investigated issues. Results: based on COVID-19 literature data, we have highlighted a few pathophysiological mechanisms, associated with virus-based cation dysmetabolism, multi-organ attack, mitochondria degeneration and ferroptosis. Our suggested elucidated pathological sequence is: a) spike protein subunit S1 docking with sialylated membrane glycoproteins/receptors (ACE2, CD147), and S2 subunit fusion with the lipid layer; b) cell membrane morpho-functional changes due to the consequent electro-chemical variations and viroporin action, which induce an altered ion channel function and intracellular cation accumulation; c) additional intracellular iron concentration due to a deregulated hepcidin-ferroportin axis, with higher hepcidin levels. Viral invasion may also affect erythrocytes/erythroid precursors, endothelial cells and macrophages, through SA and CD147 receptors, with relative hemoglobin and iron/calcium dysmetabolism. AB0 blood group, hemochromatosis, or environmental elements may represent possible factors which affect individual susceptibility to COVID-19. Conclusions: our literature analysis confirms the combined role of SA molecules, ACE2, CD147, viroporins and hepcidin in determining the cation dysmetabolism and final ferroptosis in the cells infected by SARS-CoV-2. The altered ion channels and electrochemical gradients of the cell membrane have a pivotal role in the virus entry and cell dysmetabolism, with subsequent multi-organ immune-inflammatory degeneration and erythrocyte/hemoglobin alterations.

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DCcov: Repositioning of drugs and drug combinations for SARS-CoV-2 infected lung through constraint-based modeling

Cited by 20 publications

References 94 publications

FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations

FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations

Context-Specific Genome-Scale Metabolic Modelling and Its Application to the Analysis of COVID-19 Metabolic Signatures

COVID-19, Cation Dysmetabolism, Sialic Acid, CD147, ACE2, Viroporins, Hepcidin and Ferroptosis: A Possible Unifying Hypothesis

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