Lithospermic acid inhibits dengue virus infection through binding with envelope proteins.

The dengue virus has emerged as a global pandemic, highlighting the urgent need for the immediate development of antiviral therapeutics. Lithospermum erythrorhizon, a medicinal plant commonly used in China for various ailments including viral infections, inflammation, rheumatism, and cancer, showed promising antiviral properties in our research. Specifically, both the ethanol extract of Lithospermum erythrorhizon and its active component, lithospermic acid, demonstrated significant inhibitory effects on Dengue virus (DENV) replication in Vero cells, with EC50 values of 6.50 μg/mL(95 % CI: 2.25 to 18.98)and 15.00 μM(95 % CI: 12.13 to 18.07), respectively. Notably, lithospermic acid exhibited potent antiviral activity across multiple cell lines against DENV, impeding virus replication and specifically impeding the expression of viral E and NS3 proteins during the early stages of DENV infection. Experimental assays involving RNase digestion and sucrose density gradient analysis confirmed that lithospermic acid did not directly inactivate DENV but rather interfered with viral processes. Furthermore, the compound was found to bind to the E protein of DENV, effectively inhibiting viral infection and mitigating the cytopathic effects induced by DENV. Collectively, these findings underscore the potential of lithospermic acid as a promising candidate for the development of therapeutic strategies targeting DENV infection.