A medical revolution

EMBL alumnus Raffaele De Francesco’s work on the Hepatitis C virus (HCV) led to a medical revolution. Previously, certain chronic viral infections had been kept under control using drugs, but it had never been possible to cure them completely by removing the virus from the body. De Francesco’s work allowed Hepatitis C to become the first case in the history of medicine in which a chronic viral infection was cured with direct antiviral agents.

“I wanted to find the virus’ Achilles’ heel and hit it with antiviral agents.”

Although the genome of HCV had been isolated and sequenced, finding a cure for Hepatitis C still presented a challenge. Liver cells are difficult to grow in cell culture, and the virus didn’t function as well in cultured cells as it does in the human body. It took more than a decade to find the right conditions to grow the virus in the laboratory. It was then necessary to develop biochemical tools and assays that would help researchers find ways of interfering with the virus’ enzymes – preventing it from functioning.

These technical challenges, as well as the huge medical need, pushed De Francesco to work with all the molecular biology and biochemistry tools available, to understand what each part of the virus’ genome does. “I wanted to find the virus’ Achilles’ heel and hit it with antiviral agents,” he explains.

In his lab at the Institute for Research in Molecular Biology (IRBM) in Pomezia, Italy, he identified, purified and developed in vitro assays for two viral key proteins, NS3/4A protease and NS5B polymerase. His discoveries allowed the scientific community to start screening for agents to inhibit the two viral enzymes, eventually leading to a cure for Hepatitis C.

“My work in Cortese’s group was really pivotal in starting my career as an independent scientist.”

Now Head of Virology at INGM, the National Institute for Molecular Genetics, in Milan, Italy, De Francesco is clear about what he gained from his time in Riccardo Cortese‘s group at EMBL. “Riccardo gave me a lot of guidance but at the same time enough autonomy and freedom to follow my own interests,” he explains. “My work in his group was really pivotal in starting my career as an independent scientist.”

Berta Carreño