Ginsenosides are a class of natural steroid glycosides and triterpene saponins found in Panax ginseng. After screening of a commercial ginsenoside compound library for low cellular cytotoxicity and the ability to mediate efficient reductions in hepatitis B virus (HBV) mRNA expression levels in HepG2.2.15 cells, three ginsenosides (Rg6, Rh4, and Rb3) are selected. Thereafter, using the same cellular model, all three ginsenosides are shown to mediate efficient, selective inhibition of HBV mRNA expression levels, and also interfere with the secretion of both HBV particles and hepatitis B surface antigen (HBsAg). Drug combination studies are performed in both HepG2.2.15 and HBV-infected HepG2-NTCPsec+ cell models with the selected ginsenosides and lamivudine (LMV), a nucleoside analogue used to treat chronic hepatitis B (CHB) infections. These studies, involving RT-qPCR and ELISA, suggest that Rh4/LMV combinations in particular act synergistically to inhibit the secretion of HBV particles and HBsAg. Therefore, on the assumption that appropriate in vivo data are in future agreement, Rh4, in particular, might be used in combination with nucleoside/nucleotide analogues (NUCs) to devise an effective, cost-efficient combination therapy for the treatment of patients with CHB infections.

Applied Molecular Virology Laboratory Institut Pasteur Korea 696 Sampyeong dong Bundang gu Seongnam si Gyeonggi do South Korea

Department of Chemistry and Biochemistry Mendel University in Brno Zemědělská 1665 1 CZ 613 00 Brno Czech Republic

Department of Experimental Biology Faculty of Science Masaryk University Kamenice 735 5 CZ 625 00 Brno Czech Republic

Division of Bio Medical Science and Technology University of Science and Technology Daejeon South Korea

Institute of Parasitology Biology Centre of the Czech Academy of Sciences Branišovská 1160 31 CZ 370 05 České Budějovice Czech Republic

KP Therapeutics s r o Purkyňova 649 127 CZ 612 00 Brno Czech Republic

Screening Discovery Platform Institut Pasteur Korea 696 Sampyeong dong Bundang gu Seongnam si Gyeonggi do South Korea

Veterinary Research Institute Hudcova 296 70 CZ 621 00 Brno Czech Republic

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