Andrographolide Inhibits Rabies Virus Replication

Rabies is a fatal zoonotic disease caused by infection with the rabies virus (RABV). Anti-RABV serum or antibody is a unique treatment for patients infected by RABV. However, the mortality is almost 100% in the underdeveloped regions due to the high price and the high cost of transportation and preservation of anti-RABV serum or antibody. Therefore, it is urgently needed to develop novel therapies that can effectively fight against RABV infection. Andrographolide (Andro) is a labdane diterpenoid isolated from Andrographis paniculate, which has been used to treat bacterial and viral infections for decades. In this study, we found that Andro dose-dependently inhibited RABV replication in host cells, with a half-maximal effective concentration (EC₅₀) of slightly less than 60 μmol/L. The antiviral effects of Andro were independent of viral strains and cell lines. Pretreatment of RABV with Andro in test tubes for 1 h did not affect virus replication in host cells, implying that Andro did not directly reduce RABV viability. Of interest, Andro treatment showed no influence on either RABV binding to cells or RABV invasion of cells. Also, Andro treatment downregulated the expression of RABV genomic RNA and structural genes in the cells. To investigate the therapeutic efficacy of Andro in vivo, mice were administered Andro via intraperitoneal (i.p.) injection or intragastric (i.g.) gavage. Neither the administration route nor the dosage significantly affected body weight. Notably, Andro protected mice against a lethal challenge with RABV strain challenge virus standard 11 (CVS-11). Specifically, i.p. injection of 100 mg/kg and 1 mg/kg Andro increased survival rates from 20% to 60% and 80%, respectively, while i.g. gavage of 250 mg/kg Andro elevated the survival rate from 30% to 60%. Correspondingly, RABV viral loads in mouse brain tissues were also reduced. The results suggest that Andro has great potential as a novel anti-RABV agent for the treatment of rabies.