Plant derivatives inhibit hepatitis B virus entry

Reuters Health Information: Plant derivatives inhibit hepatitis B virus entry

Plant derivatives inhibit hepatitis B virus entry

Last Updated: 2017-01-30

By David Douglas

NEW YORK (Reuters Health) - Plant-derived proanthocyanidin (PAC) and its analogs show action against hepatitis B virus, according to in vitro studies by Japanese researchers.

In fact, Dr. Senko Tsukuda told Reuters Health by email, "PAC and its analogs represent a new class of specific HBV inhibitors that are less toxic grape seed-derived agents."

In a January 17 online paper in Hepatology, Dr. Tsukuda of the Tokyo University of Science and colleagues note that in contrast to HIV and HCV which generate around 10 viral proteins, HBV requires only four viral genes for efficient replication and infection. This limits potential drug targets.

Entry prohibition might thus be a particularly rewarding approach, they say, and PAC is a natural product mainly consisting of multimeric flavanol which they found inhibits HBV entry into host cells by targeting the HBV large surface protein (LHB).

HBV enters host cells via a low affinity viral attachment to hepatocytes and a subsequent high affinity interaction with the specific receptor that can trigger viral internalization.

The team established that PAC decreased HBV infection in a dose-dependent manner as monitored by the level of HBs antigen secreted from infected primary human hepatocytes. There was no significant cytotoxicity.

PAC directly interacted with the area essential for receptor binding in the preS1 region in the LHBs protein.

"Importantly," the investigators point out, "PAC had a pan-genotypic anti-HBV activity and was also effective against a clinically relevant nucleoside analog-resistant HBV isolate."

They further found that co-treatment with PAC augmented the ability of the nucleoside analog tenofovir to interrupt HBV spread over time in primary human hepatocytes.

These findings, the researchers conclude, "strongly encourage further analysis of PAC derivatives for the development of a novel class of anti-HBV agents."


Hepatology 2017.

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