Treatment with Erythromycin and Kampo medicine (Keigai-rengyo-to, Seijo-bofu-to, or Bofu-tsusho-san) for Japanese encephalitis virus infection

抄録

Japanese encephalitis virus (JEV), a mosquito‑borne Flavivirus, is a major cause of severe encephalitis in humans. Its ~11‑kb positive‑sense RNA genome encodes a single polyprotein that is cleaved into structural proteins (C, prM, E) forming the viral particle and seven non‑structural proteins involved in replication, assembly, and immune evasion. JEV causes an estimated 69,000 infections annually, with mortality reaching 30% and nearly half of survivors experiencing long‑term neurological or psychiatric damage. Although vaccines such as JE‑VAX, SA14‑14‑2, and Vero cell–derived formulations are widely used, about 80% of cases still occur in vaccinated regions, suggesting gaps in immunization strategies or vaccine limitations. No antiviral drug has shown clear clinical efficacy, though several candidates—including manidipine, ribavirin, interferon, bortezomib, and minocycline (MIN)—have demonstrated partial benefits in preclinical or limited clinical studies. Recently, combinations of MIN with Japanese Kampo medicines (KMs) have gained attention for antiviral potential. Ingredients in KMs such as Scutellariae Radix, Schizonepetae Spica, Forsythiae Fructus, and Rhei Rhizoma contain compounds (e.g., baicalein, luteolin, rosmarinic acid, kaempferol, aloe‑emodin) with demonstrated anti‑JEV or anti‑inflammatory activity. Among the formulations examined, Bofu‑tsusho‑san (BTS) may offer particularly strong antiviral potential, though Keigai-rengyo-to (KRT) and Seijo‑bofu‑to (SBT) also contain relevant bioactive components. Further clinical trials are needed to evaluate the safety and efficacy of MIN–KM combination therapy.