CNRS scientists uncover activation mechanism of bemnifosbuvir

CNRSAug 28 2024

CNRS Scientists have deciphered the activation pathway of bemnifosbuvir, a drug candidate initially in development to treat hepatitis C virus (HCV). The findings of the research team, led by CNRS scientists, unlock new opportunities to boost the efficacy of this type of drug against other RNA viruses, such as the ones that cause Covid-19 and dengue fever.

When taken in pill form, bemnifosbuvir - like all antivirals in the same family - must undergo a series of changes inside infected cells before it acquires the form needed to prevent a virus from multiplying.

Scientists have discovered that five different enzymes drive this series of changes. They used X-ray crystallization techniques to study the three-dimensional structure of these enzymes and their surfaces interacting with the drug. Scientists also converged on the chemical parts of bemnifosbuvir behind its enhanced efficacy in liver cells. This discovery is a step towards improving the drug potency in other infected organs, such as the lungs in the case of Covid-19.

The findings, published in PLOS Biology on 27 August 2024 are expected to expand control over the nucleotide analogue activation pathway and encourage the development of novel compounds expanding effectiveness against other RNA viruses. Similarly, it will facilitate accurate prediction of which cell-type activates which antiviral drug candidate. Scientists can also use this new knowledge to limit clinical trials to animal models that in fact have the enzymes needed to activate this type of drug.