COVID-19, hepatitis C: towards effective drugs

Bemnifosbuvir is a molecule developed by the American company Atea Pharmaceuticals. Initially in development to fight the HCV virus that causes hepatitis C, the drug candidate was also found to be active against SARS-CoV-2, the virus that causes COVID-19. Bemnifosbuvir is currently in Phase 2 development for HCV and Phase 3 development for COVID-19.

Enhanced efficacy

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 to the chemical parts in 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.

Better control of drug activation

These findings, published in PLOS Biology on August 27, 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 activate 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.