Antiviral activity of Saponin C from Liriope muscari against influenza A virus and SARS-CoV-2.

Saponin C (also known as DT-13) is the dominant ingredient extracted from the tuber of Liriope muscari (Decne.) L. H. Bailey, which exhibits multiple pharmacological activities, including anti-tumor, anti-thrombotic, cardioprotective and anti-inflammatory effects. However, its antiviral potential remains unexplored. This study aimed to investigate the inhibitory activity and underlying mechanisms of Saponin C against both influenza A virus (IAV) and SARS-CoV-2. In vitro experiments demonstrated that Saponin C dose-dependently inhibited IAV replication in MDCK and A549 cells. Time-of-addition assay revealed that Saponin C targeted the post-entry stages of IAV replication by impairing viral ribonucleoprotein (vRNP) function. This was evidenced by the suppression of viral polymerase activity, reduction of viral RNA synthesis, and delayed nuclear export of vRNP. The in vivo efficacy was further validated in a lethal H1N1 mouse model, where both prophylactic and therapeutic administration of Saponin C significantly improved the survival rate of infected mice, reduced viral loads in lung tissues, and attenuated virus-induced pulmonary inflammation in a dose-dependent manner. Beyond IAV, Saponin C also effectively inhibited SARS-CoV-2 infection by blocking viral entry, specifically through interfering with the binding of viral spike protein to the human ACE2 receptor and suppressing spike-mediated membrane fusion. Collectively, these findings demonstrate that Saponin C possesses antiviral potential against IAV and SARS-CoV-2, and may thus serve as a promising therapeutic agent for the treatment of respiratory viral infections.