Comparative evaluation of flavonoids reveals the superiority and promising inhibition activity of silibinin against SARS‐CoV‐2
Rania Hamdy, Ahmed Mostafa, Noura M. Abo Shama, Sameh S. M. Soliman, Bahgat Fayed
Abstract
Abstract Flavonoids are phenolic compounds naturally found in plants and commonly consumed in diets. Herein, flavonoids were sequentially evaluated by a comparative in silico study associated with systematic literature search. This was followed by an in vitro study and enzyme inhibition assays against vital SARS‐CoV‐2 proteins including spike (S) protein, main protease (M pro ), RNA‐dependent RNA‐polymerase (RdRp), and human transmembrane serine protease (TMPRSS2). The results obtained revealed 10 flavonoids with potential antiviral activity. Out of them, silibinin showed promising selectivity index against SARS‐CoV‐2 in vitro. Screening against S protein discloses the highest inhibition activity of silibinin. Mapping the activity of silibinin indicated its excellent binding inhibition activity against SARS‐CoV‐2 S protein, M pro and RdRP at IC 50 0.029, 0.021, and 0.042 μM, respectively, while it showed no inhibition activity against TMPRSS2 at its IC 50(SARS‐CoV‐2) . Silibinin was tested safe on human mammalian cells at >7‐fold its IC 50(SARS‐CoV‐2) . Additionally, silibinin exhibited >90% virucidal activity at 0.031 μM. Comparative molecular docking (MD) showed that silibinin possesses the highest binding affinity to S protein and RdRP at −7.78 and −7.15 kcal/mol, respectively. MDs showed that silibinin exhibited stable interaction with key amino acids of SARS‐CoV‐2 targets. Collectively, silibinin, an FDA‐approved drug, can significantly interfere with SARS‐CoV‐2 entry and replication through multi‐targeting activity.