Two drugs, acting in ‘synergy’ with each other, may perhaps be the answer to treat the virulent hepatitis C disease. Though the severe liver disease affects more than 20 crore people worldwide — with nearly 400,000 deaths recorded annually — there is currently no vaccine for the disease. Treatment comprises multiple drugs, with little understanding into the dosage required for the combinations.
However, a recent study by researchers of the Indian Institute of Science (IISc), Bengaluru suggests a breakthrough: by modelling the complementary actions of drugs that can eventually effectively target the hepatitis C virus (HCV) pathways.
Narendra Dixit and his team from the Department of Chemical Engineering, IISc — who have been researching into the virus for over a decade — looked into the reasons for the synergy between HCV entry inhibitors (EIs) and antiviral drugs used for treating the various stages of the disease. This synergy was poorly understood as the entry inhibitors work in tandem with a number of drugs and pathways, making it difficult to pinpoint exactly how it works.
In the study published in CPT Pharmacometrics and Systems Pharmacology, Prof. Dixit’s team constructed mathematical and computational models to hypothesise that the working-in-tandem was due to the interactions of the drugs and the cells and not between the drugs as previously thought. In a cell population, the entry inhibitors inhibit the entry of HCV into cells with low receptors; while, in cells with high receptor levels, the antiviral drugs act. By day 3 postinfection, 90 per cent inhibition was achieved, notes the study.In effect, treatment of HCV can be done not by looking at the drugs, but by looking at the target cells. “While designing drug combinations, target heterogeneity (varieties in the cell) would be an important factor to account for. It doesn’t matter what you target, it looks like the drugs will act in synergy if their target levels vary from cell to cell,” says Prof. Dixit.
"This view will change the combinations and dosages in which drugs are administered; and the study could be extended for bacterial, viral or even cancer-related pathologies, " he says.
