Fruitful Study: Compound in Plums Inhibits Hepatitis C Virus Entry

A flavonoid called rutin inhibited HCV-like particles from binding to hepatoma cells and inhibited HCV from entering the cells during the virus’s initial entry stage.

Researchers in India have discovered that a naturally occurring compound in plums blocks the entry of hepatitis C virus (HCV) into cultured liver cells. The finding may have positive implications for developing new drugs to treat the liver-attacking disease, the scientists said.

The team 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.

“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,” the authors wrote.

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, three of the items exhibited toxicity to liver culture cells and were abandoned. Of the four 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.

The researchers discovered a single compound with more than 90% purity. They used tests including nuclear magnetic resonance (NMR) 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. They added it different stages of viral infection 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.

The scientists noted that their discovery may expand current thinking on hepatitis C therapies. Most of today’s direct-acting antiviral (DAA) 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. Further, current HVC drugs are expensive and may not be well tolerated, the team said.

“Therefore, combination of inhibitors targeting different stages of the virus lifecycle including entry, replication and assembly/secretion might be a better therapeutic strategy,” the researchers concluded.

The study, “Identification of a flavonoid isolated from plum (Prunus domestica) as a potent inhibitor of Hepatitis C virus entry,” was published online in Nature.com’s Scientific Reports.

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