Comparative Antiviral Activity of Aqueous and Ethanolic Extract from Salvia miltiorrhiza against Feline Calicivirus, as a Surrogate for Human Norovirus

Background: Feline calicivirus (FCV), a surrogate for human norovirus, was used to evaluate the antiviral activity of aqueous (SM-DW) and ethanolic (SM-E) extracts of Salvia miltiorrhiza. In the absence of effective antivirals against non-enveloped RNA viruses, such as noroviruses, screening traditional medicinal plants, such as S. miltiorrhiza, provides valuable insights for developing natural antiviral agents. Methods and Results: The cytotoxicity and maximal non-cytotoxic concentrations of both extracts were assessed in Crandell-Rees feline kidney cells. SM-E showed markedly stronger antiviral activity, inhibiting FCV replication at 3.13 ㎍/㎖, whereas SM-DW required 100 ㎍/㎖ to achieve a similar effect, indicating more than a 30-fold increase in potency. Additionally, SM-E exhibited a higher plaque reduction rate and greater suppression of viral titers, particularly in post-infection treatment, suggesting potential interference with intracellular viral replication. High-performance liquid chromatography revealed that SM-E contained substantially higher levels of lipophilic diterpenoids, especially tanshinone IIA, than SM-DW. This enriched composition appeared to be closely linked to the enhanced antiviral efficacy of SM-E, indicating that tanshinone IIA may be the key active constituent responsible for viral inhibition. Conclusions: These results indicate that the choice of the extraction solvent critically affects the antiviral potential of S. miltiorrhiza and highlight SM-E as a promising natural antiviral candidate against noroviruses, acting through tanshinone-enriched mechanisms.