scholarly journals Network Pharmacology Study on Morus alba L. Leaves: Pivotal Functions of Bioactives on RAS Signaling Pathway and Its Associated Target Proteins against Gout

2021 ◽  
Vol 22 (17) ◽  
pp. 9372
Author(s):  
Ki-Kwang Oh ◽  
Md. Adnan ◽  
Dong-Ha Cho
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Gouty Arthritis ◽  
Gene Set Enrichment Analysis ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Ras Signaling ◽  
Target Proteins ◽  
Lipinski’S Rule ◽  
Ras Signaling Pathway

M. alba L. is a valuable nutraceutical plant rich in potential bioactive compounds with promising anti-gouty arthritis. Here, we have explored bioactives, signaling pathways, and key proteins underlying the anti-gout activity of M. alba L. leaves for the first-time utilizing network pharmacology. Bioactives in M. alba L. leaves were detected through GC-MS (Gas Chromatography-Mass Spectrum) analysis and filtered by Lipinski’s rule. Target proteins connected to the filtered compounds and gout were selected from public databases. The overlapping target proteins between bioactives-interacted target proteins and gout-targeted proteins were identified using a Venn diagram. Bioactives-Proteins interactive networking for gout was analyzed to identify potential ligand-target and visualized the rich factor on the R package via the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway on STRING. Finally, a molecular docking test (MDT) between bioactives and target proteins was analyzed via AutoDock Vina. Gene Set Enrichment Analysis (GSEA) demonstrated that mechanisms of M. alba L. leaves against gout were connected to 17 signaling pathways on 26 compounds. AKT1 (AKT Serine/Threonine Kinase 1), γ-Tocopherol, and RAS signaling pathway were selected as a hub target, a key bioactive, and a hub signaling pathway, respectively. Furthermore, three main compounds (γ-Tocopherol, 4-Dehydroxy-N-(4,5-methylenedioxy-2-nitrobenzylidene) tyramine, and Lanosterol acetate) and three key target proteins—AKT1, PRKCA, and PLA2G2A associated with the RAS signaling pathway were noted for their highest affinity on MDT. The identified three key bioactives in M. alba L. leaves might contribute to recovering gouty condition by inactivating the RAS signaling pathway.

scholarly journals Network pharmacology of bioactives from Sorghum bicolor with targets related to diabetes mellitus

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0240873
Author(s):  
Ki Kwang Oh ◽  
Md. Adnan ◽  
Dong Ha Cho
Keyword(s):  
Diabetes Mellitus ◽  
Sorghum Bicolor ◽  
Signaling Pathway ◽  
Gene Set Enrichment Analysis ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Overlapping Genes ◽  
Lipinski’S Rule ◽  
Ppar Signaling ◽  
Promising Source

Background Sorghum bicolor (SB) is rich in protective phytoconstituents with health benefits and regarded as a promising source of natural anti-diabetic substance. However, its comprehensive bioactive compound(s) and mechanism(s) against type-2 diabetes mellitus (T2DM) have not been exposed. Hence, we implemented network pharmacology to identify its key compounds and mechanism(s) against T2DM. Methods Compounds in SB were explored through GC-MS and screened by Lipinski’s rule. Genes associated with the selected compounds or T2DM were extracted from public databases, and the overlapping genes between SB-compound related genes and T2DM target genes were identified using Venn diagram. Then, the networking between selected compounds and overlapping genes was constructed, visualized, and analyzed by RStudio. Finally, affinity between compounds and genes was evaluated via molecular docking. Results GC-MS analysis of SB detected a total of 20 compounds which were accepted by the Lipinski’s rule. A total number of 16 compounds-related genes and T2DM-related genes (4,763) were identified, and 81 overlapping genes between them were selected. Gene set enrichment analysis exhibited that the mechanisms of SB against T2DM were associated with 12 signaling pathways, and the key mechanism might be to control blood glucose level by activating PPAR signaling pathway. Furthermore, the highest affinities were noted between four main compounds and six genes (FABP3-Propyleneglyco monoleate, FABP4-25-Oxo-27-norcholesterol, NR1H3-Campesterol, PPARA-β-sitosterol, PPARD-β-sitosterol, and PPARG-β-sitosterol). Conclusion Our study overall suggests that the four key compounds detected in SB might ameliorate T2DM severity by activating the PPAR signaling pathway.

scholarly journals Network Pharmacology Identifies the Mechanisms of Sang-Xing-Zhi-Ke-Fang against Pharyngitis

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yinhe Deng ◽  
Quanjiang Li ◽  
Menglin Li ◽  
Tiantian Han ◽  
Guixian Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Influenza A ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Ras Signaling ◽  
Clinical Effects ◽  
Overlapping Genes

Background. Sang-Xing-Zhi-Ke-Fang (SXZKF) demonstrates good therapeutic effect against pharyngitis. Nevertheless, the pharmacological mechanism underlying its effectiveness is still unclear. Objective. To investigate the underlying mechanisms of SXZKF against pharyngitis using network pharmacology method. Methods. Bioactive ingredients of SXZKF were collected and screened using published literature and two public databases. Using four public databases, the overlapping genes between these bioactive compound-related and pharyngitis-related genes were identified by Venn diagram. Protein-protein interaction (PPI) was obtained using “Search Tool for the Retrieval of Interacting Genes (STRING)” database. “Database for Annotation, Visualization, and Integrated Discovery ver. 6.8 (DAVID 6.8)” was used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to explore the molecular mechanisms of SXZKF against pharyngitis. Finally, Cytoscape 3.7.2 software was used to construct and visualize the networks. Result. A total of 102 bioactive compounds were identified. Among them, 886 compounds-related and 6258 pharyngitis-related genes were identified, including 387 overlapping genes. Sixty-three core targets were obtained, including ALB, PPARγ, MAPK3, EGF, and PTGS2. Signaling pathways closely related to mechanisms of SXZKF for pharyngitis were identified, including serotonergic synapse, VEGF signaling pathway, Fc epsilon RI signaling pathway, Ras signaling pathway, MAPK signaling pathway, and influenza A. Conclusion. This is the first identification of in-depth study of SXZKF against pharyngitis using network pharmacology. This new evidence could be informative in providing new support on the clinical effects of SXZKF on pharyngitis and for the development of personalized medicine for pharyngitis.

scholarly journals Elucidating Drug-Like Compounds and Potential Mechanisms of Corn Silk (Stigma Maydis) against Obesity: A Network Pharmacology Study

2021 ◽  
Vol 43 (3) ◽  
pp. 1906-1936
Author(s):  
Ki-Kwang Oh ◽  
Md. Adnan ◽  
Dong-Ha Cho
Keyword(s):  
Native Americans ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Protein S ◽  
Gas Chromatography Mass Spectrometry ◽  
Network Pharmacology ◽  
Bioactive Constituents ◽  
Lipinski’S Rule ◽  
Protein Protein Interaction ◽  
Corn Silk

Corn silk (Stigma Maydis) has been utilized as an important herb against obesity by Chinese, Korean, and Native Americans, but its phytochemicals and mechanisms(s) against obesity have not been deciphered completely. This study aimed to identify promising bioactive constituents and mechanism of action(s) of corn silk (CS) against obesity via network pharmacology. The compounds from CS were identified using Gas Chromatography Mass Spectrometry (GC-MS) and were confirmed ultimately by Lipinski’s rule via SwissADME. The relationships of the compound-targets or obesity-related targets were confirmed by public bioinformatics. The signaling pathways related to obesity, protein-protein interaction (PPI), and signaling pathways-targets-bioactives (STB) were constructed, visualized, and analyzed by RPackage. Lastly, Molecular Docking Test (MDT) was performed to validate affinity between ligand(s) and protein(s) on key signaling pathway(s). We identified a total of 36 compounds from CS via GC-MS, all accepted by Lipinski’s rule. The number of 36 compounds linked to 154 targets, 85 among 154 targets related directly to obesity-targets (3028 targets). Of the final 85 targets, we showed that the PPI network (79 edges, 357 edges), 12 signaling pathways on a bubble chart, and STB network (67 edges, 239 edges) are considered as therapeutic components. The MDT confirmed that two key activators (β-Amyrone, β-Stigmasterol) bound most stably to PPARA, PPARD, PPARG, FABP3, FABP4, and NR1H3 on the PPAR signaling pathway, also, three key inhibitors (Neotocopherol, Xanthosine, and β-Amyrone) bound most tightly to AKT1, IL6, FGF2, and PHLPP1 on the PI3K-Akt signaling pathway. Overall, we provided promising key signaling pathways, targets, and bioactives of CS against obesity, suggesting crucial pharmacological evidence for further clinical testing.

scholarly journals Therapeutic mechanism of Toujie Quwen granules in COVID-19 based on network pharmacology

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Ying Huang ◽  
Wen-jiang Zheng ◽  
Yong-shi Ni ◽  
Mian-sha Li ◽  
Jian-kun Chen ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Integrated Network ◽  
Therapeutic Mechanism ◽  
The World

Abstract Background Chinese medicine Toujie Quwen granule (TJQW) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases by relieving symptoms, slowing the progression of the disease, and boosting the recovery of patients. But the bioactive compounds and potential mechanisms of TJQW for COVID-19 prevention and treatment are unclear. This study aimed to explore the potential therapeutic mechanism of TJQW in coronavirus disease 2019 (COVID-19) based on an integrated network pharmacology approach. Methods TCMSP were used to search and screen the active ingredients in TJQW. The Swiss TargetPrediction was used to predict the potential targets of active ingredients. Genes co-expressed with ACE2 were considered potential therapeutic targets on COVID-19. Venn diagram was created to show correlative targets of TJQW against COVID-19. Cytoscape was used to construct a “drug-active ingredient-potential target” network, STRING were used to construct protein-protein interaction network, and cytoHubba performed network topology analysis. Enrichment of biological functions and signaling pathways of core targets was performed by using the clusterProfiler package in R software and ClueGO with CluePedia plugins in Cytoscape. Results A total of 156 active ingredients were obtained through oral bioavailability and drug-likeness screenings. Two hundred twenty-seven potential targets of TJQW were related to COVID-19. The top ten core targets are EGFR, CASP3, STAT3, ESR1, FPR2, F2, BCL2L1, BDKRB2, MPO, and ACE. Based on that, we obtained 19 key active ingredients: umbelliprenin, quercetin, kaempferol, luteolin, praeruptorin E, stigmasterol, and oroxylin A. And the enrichment analysis obtained multiple related gene ontology functions and signaling pathways. Lastly, we constructed a key network of “drug-component-target-biological process-signaling pathway”. Our findings suggested that TJQW treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including regulation of inflammatory response, viral process, neutrophil mediated immunity, PI3K-Akt signaling pathway, MAPK signaling pathway, Jak-STAT signaling pathway, Complement and coagulation cascades, and HIF-1 signaling pathway. Conclusions Our study uncovered the pharmacological mechanism underlying TJQW treatment for COVID-19. These results should benefit efforts for people around the world to gain more knowledge about Chinese medicine TJQW in the treatment of this vicious epidemic COVID-19, and help to address this pressing problem currently facing the world.

scholarly journals A network pharmacology analysis on drug-like compounds from Ganoderma lucidum for alleviation of Atherosclerosis

2021 ◽  
Author(s):  
Ki Kwang Oh ◽  
Md. Adnan ◽  
Dong Ha Cho
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Ganoderma Lucidum ◽  
Mapk Signaling ◽  
Mendelian Inheritance ◽  
Chronic Inflammatory Disease ◽  
Mapk Signaling Pathway ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Overlapping Genes

Abstract Background: Ganoderma lucidum (GL) is known as a potent alleviator against chronic inflammatory disease like atherosclerosis (AS), but its critical bioactive compounds and their mechanisms against AS have not been unveiled. This research aimed to identify the key compounds(s) and mechanism(s) of GL against AS through network pharmacology.Methods: The compounds from GL were identified by gas chromatography-mass spectrum (GC-MS), and SwissADME screened their physicochemical properties. Then, the gene(s) associated with the screened compound(s) or AS related genes were identified by public databases, and we selected the overlapping genes using a Venn diagram. The networks between overlapping genes and compounds were visualized, constructed, and analyzed by RStudio. Finally, we performed molecular docking test (MDT) to identify key gene(s), compound(s) on AutoDockVina.Results: A total of 35 compounds in GL was detected via GC-MS, and 34 compounds (accepted by the Lipinski's rule) were selected as drug-like compounds (DLCs). A total of 34 compounds were connected to the number of 785 genes and 2,606 AS-related genes were identified by DisGeNET and Online Mendelian Inheritance in Man (OMIM). The final 98 overlapping genes were extracted between the compounds-genes network and AS-related genes. On Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, the number of 27 signaling pathways were sorted out, and a hub signaling pathway (MAPK signaling pathway), a core gene (PRKCA), and a key compound (Benzamide, 4-acetyl-N-(2,6-dimethylphenyl)) were selected among the 27 signaling pathways via MDT. Conclusion: Overall, we found that the identified 3 DLCs from GL have potent anti-inflammatory efficacy, improving AS by inactivating the MAPK signaling pathway.

scholarly journals Network Pharmacology-Based Prediction of the Active Compounds, Potential Targets, and Signaling Pathways Involved in Danshiliuhao Granule for Treatment of Liver Fibrosis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Yueying Tao ◽  
Kunming Tian ◽  
Ji Chen ◽  
Danfeng Tan ◽  
Yan Liu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Target Genes ◽  
Process Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Ras Signaling ◽  
Active Ingredients ◽  
Active Compounds

This study aims to predict the active ingredients, potential targets, signaling pathways and investigate the “ingredient-target-pathway” mechanisms involved in the pharmacological action of Danshiliuhao Granule (DSLHG) on liver fibrosis. Pharmacodynamics studies on rats with liver fibrosis showed that DSLHG generated an obvious anti-liver fibrosis action. On this basis, we explored the possible mechanisms underlying its antifibrosis effect using network pharmacology approach. Information about compounds of herbs in DSLHG was collected from TCMSP public database and literature. Furthermore, the oral bioavailability (OB) and drug-likeness (DL) were screened according to ADME features. Compounds with OB≥30% and DL≥0.18 were selected as active ingredients. Then, the potential targets of the active compounds were predicted by pharmacophore mapping approach and mapped with the target genes of the specific disease. The compound-target network and Protein-Protein Interaction (PPI) network were built by Cytoscape software. The core targets were selected by degree values. Furthermore, GO biological process analysis and KEGG pathway enrichment analysis were carried out to investigate the possible mechanisms involved in the anti-hepatic fibrosis effect of DSLHG. The predicted results showed that there were 108 main active components in the DSLHG formula. Moreover, there were 192 potential targets regulated by DSLHG, of which 86 were related to liver fibrosis, including AKT1, EGFR, and IGF1R. Mechanistically, the anti-liver fibrosis effect of DSLHG was exerted by interfering with 47 signaling pathways, such as PI3K-Akt, FoxO signaling pathway, and Ras signaling pathway. Network analysis showed that DSLHG could generate the antifibrosis action by affecting multiple targets and multiple pathways, which reflects the multicomponent, multitarget, and multichannel characteristics of traditional Chinese medicine and provides novel basis to clarify the mechanisms of anti-liver fibrosis of DSLHG.

scholarly journals Resistance Mechanisms to SYK Inhibition in AML

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2638-2638 ◽  
Author(s):  
Anjali Cremer ◽  
Jana M Ellegast ◽  
Yana Pikman ◽  
Gabriela Alexe ◽  
Linda Ross ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Resistance Mechanisms ◽  
Gene Set Enrichment Analysis ◽  
Ras Signaling ◽  
Ras Pathway ◽  
Mek Inhibition ◽  
Ras Signaling Pathway ◽  
Syk Inhibitor

Abstract Alterations in signaling pathways are critical to the pathogenesis of acute myeloid leukemia (AML) and are often driven by aberrant kinases. We previously identified spleen tyrosine kinase (SYK), a non-receptor, cytoplasmic tyrosine kinase, as a druggable target in AML and a critical regulator of FLT3, the most commonly mutated receptor tyrosine kinase in this disease. SYK was initially described as having an important role in B-cell development. More recent studies showed a broader relevance of SYK in hematopoietic signaling. Multiple orally bioavailable SYK inhibitors, including entospletinib (GS-9973) and TAK-659, are currently in Phase I/II clinical trials in patients with AML, with promising results. Targeted therapy, however, is typically associated with the emergence of resistance, and combination therapy is almost always needed for a durable therapeutic response. The aim of our study, therefore, was to identify resistance mechanisms to SYK inhibition in AML and to identify new synergistic drug combinations to overcome them. We conducted a genome-scale, pooled open reading frame (ORF) library screen to investigate the mechanisms of drug resistance to SYK inhibition. We screened the AML cell lines MV4;11 and MOLM-14, which are both highly sensitive to SYK inhibitors, with entospletinib after transduction with the ORF library. Expression of KRAS and HRAS ORFs, as well as other RAS signaling pathway-related proteins, emerged as conferring the strongest resistance to entospletinib in both cell lines. Upon overexpression of NRAS and KRAS in MV4;11 and MOLM-14 cells, both wildtype for RAS, we observed i) upregulation of phospho ERK 1/2, indicating activated RAS signaling, and ii) we confirmed markedly reduced sensitivity to entospletinib. We next screened 12 AML cell lines for sensitivity to entospletinib and found that the presence of activating mutations of the RAS signaling pathway was associated with innate resistance to entospletinib. To further study the mechanism of resistance to SYK inhibition, we generated entospletinib resistant cell lines by exposing MV4;11 cells to increasing concentrations of the drug for five months. In these cells, the entospletinib IC50 shifted from 500 nM to 5 μM, and these cells were also cross resistant to the SYK inhibitor PRT062607. RNA-sequencing showed increased expression of NRAS, KRAS and related pathway genes in entospletinib resistant compared to sensitive parental cells. Accordingly, gene set enrichment analysis revealed significant upregulation of RAS signaling-related gene sets. These findings were confirmed by qPCR and western blot analysis, supporting that the activation of the RAS/MAPK signaling pathway also confers acquired resistance to SYK inhibition in AML. Because RAS mutant AML cells have been reported to be sensitive to MEK inhibition, we next tested whether MEK inhibition using PD0325901 would recapture response to SYK inhibition in RAS/MAPK activated AML cells. Indeed, entospletinib was synergistic with PD0325901 in the MV4;11 entospletinib resistant cells. Moreover, entospletinib was synergistic with PD0325901 in five different AML cell lines, including AML cell lines with RAS pathway mutations. Additionally, this drug combination was synergistic when tested in a patient sample with NRAS G12D, KRAS G12D and PTPN11 G60V mutations. In conclusion, we found that RAS pathway activation results in resistance to entospletinib in AML that may be overcome with the combination of a SYK inhibitor with a MEK inhibitor. Disclosures No relevant conflicts of interest to declare.

scholarly journals Network Pharmacology-Based Study to Uncover Potential Pharmacological Mechanisms of Korean Thistle (Cirsium japonicum var. maackii (Maxim.) Matsum.) Flower against Cancer

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5904
Author(s):  
Ki-Kwang Oh ◽  
Md. Adnan ◽  
Dong-Ha Cho
Keyword(s):  
Methyl Ester ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Akt Signaling Pathway ◽  
Anti Cancer ◽  
Cirsium Japonicum ◽  
Folk Remedies

Cirsium japonicum var. maackii (Maxim.) Matsum. or Korean thistle flower is a herbal plant used to treat tumors in Korean folk remedies, but its essential bioactives and pharmacological mechanisms against cancer have remained unexplored. This study identified the main compounds(s) and mechanism(s) of the C. maackii flower against cancer via network pharmacology. The bioactives from the C. maackii flower were revealed by gas chromatography-mass spectrum (GC-MS), and SwissADME evaluated their physicochemical properties. Next, target(s) associated with the obtained bioactives or cancer-related targets were retrieved by public databases, and the Venn diagram selected the overlapping targets. The networks between overlapping targets and bioactives were visualized, constructed, and analyzed by RPackage. Finally, we implemented a molecular docking test (MDT) to explore key target(s) and compound(s) on AutoDockVina and LigPlot+. GC-MS detected a total of 34 bioactives and all were accepted by Lipinski’s rules and therefore classified as drug-like compounds (DLCs). A total of 597 bioactive-related targets and 4245 cancer-related targets were identified from public databases. The final 51 overlapping targets were selected between the bioactive targets network and cancer-related targets. With Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, a total of 20 signaling pathways were manifested, and a hub signaling pathway (PI3K-Akt signaling pathway), a key target (Akt1), and a key compound (Urs-12-en-24-oic acid, 3-oxo, methyl ester) were selected among the 20 signaling pathways via MDT. Overall, Urs-12-en-24-oic acid, 3-oxo, methyl ester from the C. maackii flower has potent anti-cancer efficacy by inactivating Akt1 on the PI3K-Akt signaling pathway.

scholarly journals SARS-CoV-2 intervened by NSAIDs: A network pharmacology approach to decipher signaling pathway and interactive genes

2020 ◽  
Author(s):  
Ki Kwang Oh ◽  
Md. Adnan ◽  
Dong Ha Cho
Keyword(s):  
Signaling Pathway ◽  
Binding Affinity ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Ras Signaling ◽  
Overlapping Genes ◽  
Anti Inflammatory

Abstract Background: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) showed promising clinical efficacy toward COVID-19 patients as painkillers and anti-inflammatory agents. However, the prospective anti-COVID-19 mechanisms of NSAIDs are not evidently exposed. Therefore, we intended to decipher the most potent NSAIDs candidate(s) and its novel mechanism(s) against COVID-19 by network pharmacology.Method: FDA (U.S. Food & Drug Administration) approved twenty NSAIDs were used for this study. Genes related to selected NSAIDs and COVID-19 related genes were identified by the Similarity Ensemble Approach, Swiss Target Prediction, and PubChem databases. Venn diagram identified overlapping genes between NSAIDs and COVID-19 related genes. The interactive networking between NSAIDs and overlapping genes was analyzed by STRING. RStudio plotted the bubble chart of KEGG pathway enrichment analysis of overlapping genes. Finally, the binding affinity of NSAIDs against target genes was determined through molecular docking analysis.Results: Geneset enrichment analysis exhibited 26 signaling pathways against COVID-19. Inhibition of proinflammatory stimuli of tissues and/or cells by inactivating RAS signaling pathway was identified as the key anti-COVID-19 mechanism of NSAIDs. Besides, MAPK8, MAPK10, and BAD genes were explored as the associated genes of the RAS. Among twenty NSAIDs, 6MNA, rofecoxib, and indomethacin revealed promising binding affinity with the highest docking score against three identified genes, respectively.Conclusions: Overall, our proposed three NSAIDs (6MNA, rofecoxib, and indomethacin) might block the RAS by inactivating its associated genes, thus may alleviate excessive inflammation induced by SARS-CoV-2.

The Ras signaling pathway in Drosophila

1995 ◽  
Vol 5 (1) ◽  
pp. 44-50 ◽  
Author(s):  
David A. Wassarman ◽  
Marc Therrien ◽  
Gerald M. Rubin
Keyword(s):  
Signaling Pathway ◽  
Ras Signaling ◽  
Ras Signaling Pathway
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