Compound Found in Plums Shown to Inhibit Hepatitis C Virus Entry

A naturally occurring compound in plums has been found to block the entry of the hepatitis C virus (HCV) into cultured liver cells. This finding could have positive implications for the development of new drugs to treat the disease, which the World Health Organizations (WHO) estimates affects over 70 million individuals around the world.

The discovery was made by a team of researchers from the Indian Institute of Science in Bangalore focused on a flavonoid called rutin found in the common plum. Rutin inhibited HCV-like particles from binding to hepatoma cells and inhibited HCV from entering the cells during the virus’s initial entry stage, according to the researchers, led by Anjali A. Karande., PhD, a professor in the institute’s biochemistry department.

Speaking on the importance of studying the entry stage of the viral lifecycle, the authors wrote, “Since most of the drug development strategies target the replication stage of viral lifecycle, the identification of entry inhibitors might be crucial especially in case of liver-transplant recipients.”

To conduct their study, the team investigated a dozen fruits and vegetables including apples, grapes, garlic, dates and beetroot that contained naturally-derived extracts with previously documented liver-protective effects. The produce was bought from a local market, sliced and pulverized in a grinder to prepare it for study.

When first tested, 3 of the items exhibited toxicity to liver culture cells and were abandoned. Of the 4 fruits that showed inhibition to binding, the plum had the highest activity. The team selected that fruit for further study to identify the bioactive compound responsible for its anti-HCV properties.

They discovered a single compound in the plum with more than 90% purity and then used tests including nuclear magnetic resonance spectroscopy to identify the ingredient as rutin.

“The compound was found to significantly inhibit viral entry and infection in both, HCV-LP (in vitro) and HCV cell culture (ex vivo) systems,” the authors wrote.

The team then sought to determine how rutin worked to inhibit virus entry and discovered that the greatest protection occurred when the flavonoid was present in the cell culture medium before the virus was added.

The researchers determined that there was no protective effect once the virus-like particles had bound to the cells. Rutin also showed no benefit when researchers added and withdrew it before infection. This suggested that the flavonoid interferes with the virus’s binding step. Extremely high concentrations of rutin did not produce cellular toxicity during the testing, the team said.

According to the scientists, this discovery may expand current thinking on hepatitis C therapies. Most of today’s direct-acting antiviral drugs target the replication step of the HCV lifecycle. However, recent studies have indicated that adding entry inhibitors to these medicines has a synergistic effect on the efficiency of antiviral treatment. Furthermore, current HVC drugs are expensive and may not be well tolerated, the team said. To this end, the researchers suggest that using a combination of inhibitors that target different stages of the virus lifecycle might be a better therapeutic strategy.