Systems pharmacology-based drug discovery and active mechanism of natural products for coronavirus pneumonia (COVID-19): an example using flavonoids
Biol Med calculation. 2022 Jan 26;143:105241. doi: 10.1016/j.compbiomed.2022.105241. Online ahead of print.
BACKGROUND: Recently, the value of natural products has been widely recognized as these resources can potentially be applied to prevent and treat coronavirus disease 2019 (COVID-19) pneumonia. However, the discovery of natural drugs is problematic due to their complex composition and active mechanisms.
METHODS: This in-depth study was performed on flavonoids, which are compounds with anti-inflammatory and antiviral effects, to show drug discovery and the active mechanism of natural products in the treatment of COVID-19 via a pharmacological model of systems . 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 compound-target and target-disease network, target protein-protein interaction (PPI), MCODE analysis, Gene Ontology (GO) and Kyoto Encyclopedia Enrichment of Genes and Genomes (KEGG) pathway.
RESULTS: A total of 105 active flavonoid compounds were identified, of which 6 were major candidate compounds (quercetin, epigallocatechin-3-gallate (EGCG), luteolin, fisetin, wogonin, and licochalcone A). 152 related targets were generated based on the array construction and 7 family proteins (PTGS, GSK3β, ABC, NOS, EGFR and IL) were included as core targets. In addition, 528 GO items and 178 KEGG paths were selected by target function enrichment. Finally, molecular docking demonstrated good stability of the combination of selected flavonoids with 3CL Pro and ACEⅡ.
CONCLUSION: Natural flavonoids may enable resistance against COVID-19 by regulating inflammatory, antiviral and immune responses and repairing tissue damage. This study has scientific significance for the selective use of natural products, the enhancement of the medicinal value of flavonoids, and drug screening for the treatment of SARS-COV-2-induced COVID-19.