Systems pharmacology-based drug discovery and active mechanism of natural products for coronavirus pneumonia (COVID-19): An example using flavonoids. (April 2022)

• Record Type: Journal Article
• Authors: Wang, Bin; Ding, Yan; Zhao, Penghui; Li, Wei; Li, Ming; Zhu, Jingbo; Ye, Shuhong
• Is Part Of: Computers in biology and medicine. Volume 143(2022)
• Publication Date: 2022-04
• Subjects: Systems pharmacology -- Natural products -- Flavonoids -- COVID-19 -- Molecular docking; Medicine -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; 610.285
• DOI: 10.1016/j.compbiomed.2022.105241
• Languages: English
• ISSNs: 0010-4825

Abstract

Abstract: Background: Recently, the value of natural products has been extensively considered because these resources can potentially be applied to prevent and treat coronavirus pneumonia 2019 (COVID-19). However, the discovery of nature drugs is problematic because of their complex composition and active mechanisms. Methods: This comprehensive study was performed on flavonoids, which are compounds with anti-inflammatory and antiviral effects, to show drug discovery and active mechanism from natural products in the treatment of COVID-19 via a systems pharmacological model. First, a chemical library of 255 potential flavonoids was constructed. Second, the pharmacodynamic basis and mechanism of action between flavonoids and COVID-19 were explored by constructing a compound–target and target–disease network, targets protein-protein interaction (PPI), MCODE analysis, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Results: In total, 105 active flavonoid components were identified, of which 6 were major candidate compounds (quercetin, epigallocatechin-3-gallate (EGCG), luteolin, fisetin, wogonin, and licochalcone A). 152 associated targets were yielded based on network construction, and 7 family proteins (PTGS, GSK3β, ABC, NOS, EGFR, and IL) were included as central hub targets. Moreover, 528 GO items and 178 KEGG pathways were selected through enrichment of target functions. Lastly, molecular docking demonstrated good stability of the combination of selected flavonoids with 3CL Pro and ACEⅡ. Conclusion: Natural flavonoids could enable resistance against COVID-19 by regulating inflammatory, antiviral, and immune responses, and repairing tissue injury. This study has scientific significance for the selective utilization of natural products, medicinal value enhancement of flavonoids, and drug screening for the treatment of COVID-19 induced by SARS-COV-2. Graphical abstract: Image 1 Highlights: Network pharmacology technology was used to elucidate the action mechanism of natural flavonoids against COVID-19. A total of 105 active flavonoid components, 152 COVID-19 associated targets, 528 GO items, and 178 pathways were enriched. Molecular docking proved candidate flavonoids could as potential inhibitors of SARS-COV-2. Action mechanisms might be involved in regulating inflammatory, antiviral, immune response, and repairing tissue injury.