Persistent hepatitis C virus (HCV)
infection causes chronic
liver diseases and is a global health problem. Although the sustained virologic response rate in the treatment of genotype 1 using new triple
therapy (pegylated-
interferon,
ribavirin, and
telaprevir/
boceprevir) has been improved by more than 70%, several severe side effects such as
skin rash/
ageusia and advanced
anemia have become a problem. Under these circumstances, a new type of anti-HCV oral
drug with few side effects is needed. Our recently developed HCV
drug assay systems, including the HuH-7 cell line-derived OR6 and AH1R, and the Li23 cell line-derived ORL8 and ORL11, allow genome-length HCV RNAs (several strains of genotype 1b) encoding
renilla luciferase to replicate efficiently. Using these systems as anti-HCV candidates, we have identified numerous existing medicines that can be used against HCV with few side effects, such as
statins and
teprenon. To obtain additional anti-HCV candidates, we evaluated a number of oral health supplements, and found that the
capsule but not the liquid form of Cordyceps militaris (CM) (Ascomycotinanorth, North Chinese caterpillar fungus), which is used as a Chinese herbal medicine, exhibited moderate anti-HCV activity. In combination with
interferon-α or
ribavirin, CM exhibited an additive inhibitory effect. Among the main components of CM,
cordycepin, but not
ergosterol, contributed to the anti-HCV activity of CM. In consideration of all these results, we suggest that CM would be useful as an oral anti-HCV agent in combination with
interferon-α and/or
ribavirin.