ANTIVIRAL EFFECTS OF SAIKOSAPONINS ON HUMAN CORONAVIRUS 229E IN VITRO

Cheng, Pei‐Win; Ng, Lean‐Teik; Chiang, Lien‐Chai; Lin, Chun‐Ching

1.. Saikosaponins represent a group of oleanane derivatives, usually as glucosides, that are found in a number of plant families. Saikosaponins isolated from medicinal plants such as Bupleurum spp., Heteromorpha spp. and Scrophularia scorodonia have been reported to possess various biological activities, specifically antihepatitis, antinephritis, antihepatoma, anti‐inflammation, immunomodulation and antibacterial effects. 2.. The aim of the present study was to examine the anticoronaviral activity of saikosaponins (A, B(2), C and D) and their mode of action. Using the 2,3‐bis[2‐methoxy‐4‐nitro‐5‐sulfophenyl]‐5‐[(phenylamino) carbonyl‐2H‐tetrazolium hydroxide] (XTT) assay, results showed that all saikosaponins tested demonstrated antiviral activity at concentrations of 0.25–25 µmol/L, with the strongest activity being noted for saikosaponin B(2) (IC(50) = 1.7 ± 0.1 µmol/L). Interestingly, both saikosaponins A (50% cellular cytotoxicity (CC(50)) concentration = 228.1 ± 3.8 µmol/L; selectivity index (SI) = 26.6) and B(2) (CC(50) = 383.3 ± 0.2 µmol/L; SI = 221.9) exhibited no cytotoxic effects on target cells at concentrations that achieved antiviral activity. In the time‐of‐addition studies, saikosaponin B(2), at 6 µmol/L, significantly inhibited human coronavirus 229E infection following its addition at various time pre‐infection (−4 to −1 h), coinfection (0 h) and post‐infection (1–4 h). Furthermore, saikosaponin B(2) also showed an inhibitory effect on viral attachment and penetration. 3.. The present results indicate that saikosaponin B(2) has potent anticoronaviral activity and that its mode of action possibly involves interference in the early stage of viral replication, such as absorption and penetration of the virus.