Inhibition of influenza A virus by salvianolic acid C targeting neuraminidase and phosphorylated-STAT3.

BACKGROUND

New antiviral strategies are urgently needed, as evidenced by an increase in drug-resistant influenza A virus (IAV). Salvianolic acid C (Sal-C) is isolated from Salvia miltiorrhiza and possesses various pharmacological activities, such as anti-inflammatory and antioxidant. However, no studies on its anti-IAV activity have been reported yet.

PURPOSE: To investigate the anti-IAV effects of Sal-C through both in vitro and in vivo approaches and to elucidate its mechanisms of action.

METHODS

The anti-IAV effects of Sal-C in vitro were determined by cytopathic effect (CPE) inhibition, western blot and viral plaque assays. Western blot analysis revealed that the compound significantly reduced the expression of critical viral proteins. Neuraminidase (NA) inhibition assays and signalling pathway experiments were used to investigate the mechanism of action of Sal-C. The in vivo activity of Sal-C was evaluated using a mouse pneumonia model.

RESULTS

Sal-C can inhibit IAV proliferation in different cells and has low toxicity. Sal-C exerts its anti-IAV activity by interacting with NA and regulating phosphorylated-STAT3 (p-STAT3) and phosphorylated-AKT/phosphorylated-mTOR/phosphorylated-S6K (p-AKT/p-mTOR/p-S6K) activity. Sal-C treatment significantly improved mice survival, attenuated inflammatory symptoms, and reduced viral titers in IAV infected mice.

CONCLUSION

Sal-C exhibits significant anti-IAV activity in vitro and in vivo by acting on the viral protein NA and regulating host signalling pathways. Thus, Sal-C has potential for development as a novel anti-IAV agent.