Antiviral activities of hedera helix containing hederasaponin B and phyllanthus urinaria containing corilagin against enterovirus infections

Abstract

Enteroviruses (EV) are the positive sense (+) single stranded RNA viruses in the picornaviridae family causing several diseases to mammalian including humans. Usually, human enteroviruses (HEV) infections cause various symptoms including the hand-foot-mouth disease (HFMD), common cold, myocarditis, acute hemorrhagic conjunctivitis, encephalitis, poliomyelitis, and aseptic meningitis, etc. Especially, some EVs including enterovirus71 (EV71) and coxackievirus16 (CVA16) cause HFMD with neurological complications with death and many cases reported in many countries including big outbreaks. However, there are still no specially approved antiviral drugs and vaccines highly effective against HEV. Additionally, because many EVs cause diseases in children, the antiviral agents against HEVs should have the lower level of side effects than others. Based on these backgrounds, several materials including compounds from plant having been tested that could play a role in effective inhibition of viruses and virus-specific functions with lower level of side effects, and may avoid emergence of resistant mutant types in developing effective antiviral agents. In the efforts of finding HEV inhibitors from plant origin materials, we identified hederasaponin B and corilagin from Hedera helix and Phyllanthus urinaria, respectively showed antiviral activities against HEV including EV71 and CVA16. Especially in the current studies, hederasaponin B showed antiviral acrivities against EV71 especially at subtype C3 and C4a. C3 and C4a subtypes are major causative agent of HFMD in Asian countries including Korea. Addiotionally, corilagin showed antiviral activities against EV71 and CVA16. CVA16 is second major type causing HFMD followed by EV71 in many countries including Korea. Among EVs, Coxackievirus B3 (CVB3) is one of the major type causing myocarditis and pancreatitis at humans. CVB3 also has well established mouse infection model of pancreatitis. To identify broad use of antiviral agents against EVs, hederasaponin B and Phyllanthus urinaria extract were treated to identify the antiviral activities against CVB3 in vivo. The animal experiments were approved by the Institutional Animal Care and Use committees (IACUC) of the Korea Center for Disease Control and Prevention (KCDC). 5 week old female Balb/c mice were infected by CVB3 after administration of Hedera helix and Phyllanthus urinaria extracts. Body weight check and histological analysis of pancreara were carried out. Based on these results, the extracts of Hedera helix and Phyllanthus urinaria can be suggested to the novel therapeutic agents against EVs infections with broad-spectrum antiviral activities.