New insights into antiviral and cytotoxic potential of quercetin and its derivatives - A biochemical perspective

Quercetin, a potential polyphenolic which possesses several biological effects. The influenza virus polymerase basic 2 (PB2) subunit of RNA polymerase responsible for replication, degree of virus conservation and active target site for designing specific antivirals. The quercetin derivatives downloaded from PubChem were screened using PyRX software configured with Vina Wizard, targeted on cap-binding site of the PB2 of influenza viral RNA polymerase. Among the PubChem library (total 97,585,747 compounds), 410 quercetin derivatives were screened using molecular docking (affinity: < - 9.0 kcal) for their drug-likeness and in vitro cytopathic effect by Sulforhodamine B (SRB) assay. Among all quercetin derivatives, quercetin 3'-glucuronide (Q3G) showed strongest binding affinity towards cap-binding site of the PB2 subunit with -9.6 kcal of binding affinity and 0.00054 mM of Ki value, while quercetin 3'-glucuronide (Q7G) was presented highest anti-influenza activity with 2.10 +/- 0.05 of IC50 on influenza A/PR/8/34 virus and non-cytotoxic effect as CC50 > 100 mu g/mL.

Automated summary

Quercetin and its derivatives were screened for their potential antiviral properties targeting the cap-binding site of the influenza viral RNA polymerase PB2 subunit. Among them, quercetin 3'-glucuronide (Q3G) showed the strongest binding affinity, while quercetin 3'-glucuronide (Q7G) exhibited the highest anti-influenza activity with low cytotoxic effects.