Network pharmacology and molecular docking analysis reveals the mechanism of asiaticoside on COVID-19

Huang, Jia; Zhou, Xiaobo; Gong, Yiyi; Yang, Yali; Liu, Ke

doi:10.21037/atm-22-51

Cited by 7 publications

(3 citation statements)

References 63 publications

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“…Consistent with our finding, molecular docking revealed that asiaticoside had a high affinity with STAT3 for the treatment of the coronavirus disease 2019 (COVID-19). 51 Altogether, these results demonstrate that CE exerts relevant antiinflammatory properties via a cellular mechanism via inhibiting proinflammatory cytokines and JAK/STAT pathway in LPS-stimulated RAW 264.7 macrophages, a model for atopic dermatitis (Figure 7). Future studies employing specific inhibitors or gene knockdown approaches is needed to validate the proposed molecular mechanisms underlying the effects of CE in AD.…”

Section: Discussionmentioning

confidence: 70%

The Investigation of The Network Pharmacology and Mechanism of Action of Centella Asiatica Extract on The Atopic Dermatitis Model

Tungsukruthai,

Pochairach,

Krajarng

et al. 2023

Pharmacogn J.

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Background: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin condition which has a negative impact on children health. The well-known medicinal plant Centella asiatica extract (CE) is used in herbal skin care products to produce various pharmacological effects in dermatology. However, the molecular target of CE in suppressing inflammatory is largely unknown. Objective: the aim of this study was to examine anti-inflammatory properties and network pharmacology of CE in lipopolysaccharide (LPS)induced AD in vitro model. Method: RAW264.7 cells were pre-treated with CE and then were stimulated with LPS and then were investigated cell viability, NO production, and the levels of pro-inflammatory mediators. In addition, the Search Tool for Retrieval of Interacting Genes (STRING), SwissTargetPrediction and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to construct the defined mechanism of action and network pharmacology. Results: CE showed the potent inhibitory effects on LPS-induced NO. In addition, CE significantly suppressed the expression of iNOS and COX-2, as well as the production of IL-2, IL-6, IL-10, and TNFα. Furthermore, the network pharmacological analysis revealed the potential role of CE in biological processes such as regulating JAK/STATs pathway and inhibiting proinflammatory cytokines both of which were linked to AD pathogenesis. Conclusion: Our findings confirm our hypothesis that CE could be developed as a therapeutic therapy for atopic dermatitis due to its pharmacological action and signaling mechanism in the modulation of allergic skin inflammation.

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Section: Discussionmentioning

confidence: 70%

The Investigation of The Network Pharmacology and Mechanism of Action of Centella Asiatica Extract on The Atopic Dermatitis Model

Tungsukruthai,

Pochairach,

Krajarng

et al. 2023

Pharmacogn J.

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“…It has been noted that the gene OAS1 is an important gene influencing COVID-19 patients [66][67][68][69][70]. The gene STAT4 is the human transcriptomic factor of COVID-19 [71][72][73].…”

Section: Discussionmentioning

confidence: 99%

Identification of host genomic biomarkers from multiple transcriptomics datasets for diagnosis and therapies of SARS-CoV-2 infections

et al. 2023

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The pandemic of COVID-19 is a severe threat to human life and the global economy. Despite the success of vaccination efforts in reducing the spread of the virus, the situation remains largely uncontrolled due to the random mutation in the RNA sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which demands different variants of effective drugs. Disease-causing gene-mediated proteins are usually used as receptors to explore effective drug molecules. In this study, we analyzed two different RNA-Seq and one microarray gene expression profile datasets by integrating EdgeR, LIMMA, weighted gene co-expression network and robust rank aggregation approaches, which revealed SARS-CoV-2 infection causing eight hub-genes (HubGs) including HubGs; REL, AURKA, AURKB, FBXL3, OAS1, STAT4, MMP2 and IL6 as the host genomic biomarkers. Gene Ontology and pathway enrichment analyses of HubGs significantly enriched some crucial biological processes, molecular functions, cellular components and signaling pathways that are associated with the mechanisms of SARS-CoV-2 infections. Regulatory network analysis identified top-ranked 5 TFs (SRF, PBX1, MEIS1, ESR1 and MYC) and 5 miRNAs (hsa-miR-106b-5p, hsa-miR-20b-5p, hsa-miR-93-5p, hsa-miR-106a-5p and hsa-miR-20a-5p) as the key transcriptional and post-transcriptional regulators of HubGs. Then, we conducted a molecular docking analysis to determine potential drug candidates that could interact with HubGs-mediated receptors. This analysis resulted in the identification of top-ranked ten drug agents, including Nilotinib, Tegobuvir, Digoxin, Proscillaridin, Olysio, Simeprevir, Hesperidin, Oleanolic Acid, Naltrindole and Danoprevir. Finally, we investigated the binding stability of the top-ranked three drug molecules Nilotinib, Tegobuvir and Proscillaridin with the three top-ranked proposed receptors (AURKA, AURKB, OAS1) by using 100 ns MD-based MM-PBSA simulations and observed their stable performance. Therefore, the findings of this study might be useful resources for diagnosis and therapies of SARS-CoV-2 infections.

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“…Recent studies have identified some host factors and signaling pathways that are essential for the CoV life cycle ( 7 - 10 ). These include pathways related to cell proliferation and apoptosis, such as the ErbB and hypoxia-inducible factor 1 (HIF-1) pathways, and pathways related to innate immune responses, such as the tumor necrosis factor (TNF), nod-like receptor, and retinoic-acid-inducible gene I (RIG-I) signaling pathways ( 11 , 12 ). Among the factors in these pathways, the HIF-1 signaling pathway factor HIF-1a can mediate hypoxia signaling to inhibit SARS-CoV-2 replication and virion production ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

mLST8 is essential for coronavirus replication and regulates its replication through the mTORC1 pathway

et al. 2023

mBio

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Coronaviruses (CoVs), which pose a serious threat to human and animal health worldwide, need to hijack host factors to complete their replicative cycles. However, the current study of host factors involved in CoV replication remains unknown. Here, we identified a novel host factor, mammalian lethal with sec-13 protein 8 (mLST8), which is a common subunit of mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), and is critical for CoV replication. Inhibitor and knockout (KO) experiments revealed that mTORC1, but not mTORC2, is essential for transmissible gastroenteritis virus replication. Furthermore, mLST8 KO reduced the phosphorylation of unc-51-like kinase 1 (ULK1), a factor downstream of the mTORC1 signaling pathway, and mechanistic studies revealed that decreased phosphorylation of the mTORC1 downstream factor ULK1 promoted the activation of autophagy, which is responsible for antiviral replication in mLST8 KO cells. Then, transmission electron microscopy indicated that both mLST8 KO and autophagy activator inhibited the formation of double-membrane vesicles in early viral replication. Finally, mLST8 KO and autophagy activator treatment could also inhibit the replication of other CoVs, indicating a conserved relationship between autophagy activation and CoV replication. In summary, our work reveals that mLST8 is a novel host regulator of CoV replication, which provides new insights into the mechanism of CoV replication and can facilitate the development of broad-spectrum antiviral drugs. IMPORTANCE CoVs are highly variable, and existing CoV vaccines are still limited in their ability to address mutations in CoVs. Therefore, the need to improve our understanding of the interaction of CoVs with the host during viral replication and to find targets for drugs against CoVs is urgent. Here, we found that a novel host factor, mLST8, is critical for CoV infection. Further studies showed that mLST8 KO inhibited the mTORC1 signaling pathway, and we found that autophagy activation downstream of mTORC1 was the main cause of antiviral replication in mLST8 KO cells. Autophagy activation impaired the formation of DMVs and inhibited early viral replication. These findings deepen our understanding of the CoV replication process and provide insights into potential therapeutic applications.

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Network pharmacology and molecular docking analysis reveals the mechanism of asiaticoside on COVID-19

Cited by 7 publications

References 63 publications

The Investigation of The Network Pharmacology and Mechanism of Action of Centella Asiatica Extract on The Atopic Dermatitis Model

The Investigation of The Network Pharmacology and Mechanism of Action of Centella Asiatica Extract on The Atopic Dermatitis Model

Identification of host genomic biomarkers from multiple transcriptomics datasets for diagnosis and therapies of SARS-CoV-2 infections

mLST8 is essential for coronavirus replication and regulates its replication through the mTORC1 pathway

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