Investigation into molecular mechanisms and high-frequency core TCM for pulmonary fibrosis secondary to COVID-19 based on network pharmacology and data mining

Abstract

Background: The complication, pulmonary fibrosis (PF) secondary to COVID-19, may have a second wave of late mortality, given the huge number of individuals infected by COVID-19. However, the molecular mechanisms of PF secondary to COVID-19 haven't been fully elucidated, making the identification of novel strategies for targeted therapy challenging. This study aimed to systematically identify the molecular mechanisms and high-frequency core traditional Chinese medicine (TCM) targeting PF secondary to COVID-19 through network pharmacology and data mining. Methods:The molecular mechanisms of PF secondary to COVID-19 were identified by mapping the COVID-19 differentially expressed gene and known targets associated with PF, protein-protein interactions network analysis, and enrichment pathway analysis; then the high-frequency core TCM targeting PF secondary to COVID-19 were identified by data mining and "Key targets related to PF secondary to COVID-19 -Ingredients" and "Key ingredients-key herbs" network analysis; and last we validated the interaction between the key ingredients and key targets by molecular docking.Results: The molecular mechanisms of PF secondary to COVID-19 were mainly related to tumor necrosis factor (TNF) signaling pathway, cytokine−cytokine receptor interaction pathway, and NF−κB signaling pathway. Among these, cytokines interleukin 6 (IL-6), TNF, and IL-1β were identified as the key targets associated with PF secondary to COVID-19. The high-frequency core TCM targeting these key targets were identified, including ingredients of quercetin, epigallocatechin-3-gallate, emodin, triptolide, resveratrol, and herb of Polygonum cuspidatum. Finally, our results were validated by quercetin and resveratrol both well docked to IL-6, TNF, and IL-1β protein, with the estimated docking energy < 0 kcal/mol. Conclusions:This study identified the cytokines-related molecular mechanisms of PF secondary to COVID-19, and the high-frequency core TCM against PF by targeting IL-6, TNF, and IL-1β. Which provides new ideas for the discovery of small molecular compounds with potential therapeutic effects on PF secondary to COVID-19.

Association of TNF-α, TGF-β1, amphiregulin, IL-2, and EGFR WITH pulmonary fibrosis in COVID-19

“…These cytokines, including TNF-α, can facilitate the formation of fibroblasts which in turn can lead to collagen deposition. A study on COVID-19 differentially expressed gene known to be associated with pulmonary fibrosis has identified that the TNF signaling pathway is one of the molecular pathways of pulmonary fibrosis secondary to COVID-19 [13] .Cheng et al reported an up-regulated TNF- α gene in cells infected with SARS-CoV2 [14] . Serum values of TNF- α and sTNFR1 increased in patients with COVID-19.…”

Efficacy and mechanisms of traditional Chinese medicine for COVID-19: a systematic review

“…We predicted that 149 components had therapeutic effects on COVID-19 by molecular docking, of which 20 components had good docking scores not only with antiviral targets but also with anti-inflammatory or immune-regulating targets. The 20 components were formononetin, naringenin, bicuculline, luteolin, quercetin, astragaloside IV, kaempferol, isoquercitrin, rutin, beta-carotene, salvigenin, indirubin, baicalein, calycosin, artemetin, wogonin, rosmarinic acid, apigenin, 7-methoxy-2-methyl isoflavone and emodin [ 72 – 94 ]. The details of components and targets were shown in Additional files 7 and 8 ].…”

Evaluating the Therapeutic Mechanisms of Selected Active Compounds in Houttuynia cordata Thunb. in Pulmonary Fibrosis via Network Pharmacology Analysis

“…A549 cells were added to LPS coculture to induce EMT validating the predicted outcome of network pharmacology. Evidence showed that quercetin was well validated by its docking to IL-6, TNF, and IL-1β proteins ( Yu et al, 2021 ). These findings strikingly supported the molecular docking and experimental results of our study that quercetin may exert anti-PF effects by targeted binding to TNF.…”