| Abstrak/Abstract |
Hyper-inflammatory reactions due to cytokine storm lead to acute
respiratory distress syndrome and are responsible for COVID-19 death toll.
Thus, the pathways involved in inflammation and SARS-COV-2 replication
represent promising therapeutic targets. By employing a computational model,
we investigated the effect of plant flavonoids on pro-inflammatory proteins
(glucocorticoid receptor [GR], cyclooxygenase-2 [COX-2], and 5-lipoxygenase
[LOX] enzymes) and proteins involved in virus replication (main protease
[Mpro] and papain-like protease [PLpro]). This in silico study aimed to identify
promising flavonoids with anti-inflammatory and antiviral activities (multitarget) for combating COVID-19. The selected target proteins were Mpro (PDB
ID: 6LU7), PLpro (PDBID: 6WX4), COX-2 (PDBID: 6COX), LOX (PDBID: 6N2W),
and GR (PDBID: 1P93). We conducted molecular docking using PLANTS
software and obtained Lipinski’s “Rule-of-Five” parameters and the predicted
pharmacokinetic and toxicity profiles using the pkCSM online platform. Results
showed that two flavonoids, diosmin and hesperidin, exhibited a low binding
score and higher strength than the reference ligands for the target proteins
Mpro, PLpro, and LOX. Both compounds interacted with the amino acid
residues of the protein targets through hydrogen bonds and showed similar
binding patterns to approved drugs and native ligands. The prediction of
ADMET and drug-likeness profiles indicated that these two compounds have
low toxicity and good pharmacokinetic properties, except for the absorption
profile. Therefore, hesperidin and diosmin are promising multi-target agents
for COVID-19 treatment through inhibition of inflammatory progression and
virus replication |
