Novel technology speeds up drug discovery
Chronic hepatitis B is a severe liver infection caused by the hepatitis B virus(opens in new window) (HBV). Despite the availability of a vaccine since 1982, HBV infection still remains a serious global health issue, with more than 250 million carriers worldwide. “Chronic HBV infection is, in most cases, asymptomatic,” notes VIRO-FLOW(opens in new window) project coordinator Miquel A. Pericàs from the Institute of Chemical Research of Catalonia(opens in new window) in Spain. “Sustained liver inflammation and activation of fibrotic processes however can lead to liver fibrosis, cirrhosis and eventually hepatocellular carcinoma(opens in new window).” This serious health risk has driven the search for novel therapeutics that could completely eradicate the virus from infected liver cells.
Identifying new compounds
One area of interest in this field has been compounds called capsid assembly modulators(opens in new window) (CAMs). These have been identified as promising antiviral agents, capable of targeting HBV infection. The VIRO-FLOW project, which was undertaken with the support of the Marie Skłodowska-Curie Actions(opens in new window) programme, sought to build on this area of work. It aimed to developed fast and efficient techniques for identifying promising antiviral agents, and synthesising new classes of CAMs. The long-term goal is that this could eventually lead to the discovery and manufacture of more effective drugs to tackle hepatitis, and possibly other diseases. To achieve this, biochemical assays were optimised and developed, to identify small molecules that show promise as HBV inhibitors. The project also combined these biochemical assays with continuous flow chemistry(opens in new window), to safely and efficiently synthesise potential new HBV inhibitors. Key advantages of continuous flow technology over batch processing include cost efficiency and faster reactions. A novel automated microfluidic platform(opens in new window) for the screening and characterisation of possible CAMs was established, and a library of promising compounds developed. The success of the project has led to two patents, while other pioneering findings have been published(opens in new window) in peer reviewed articles. At the same time, the project provided cutting-edge training for three doctoral students in this field. “A key aim here was to educate the next generation of well-prepared researchers,” says Pericàs. “We wanted to provide them with the scientific, technical and entrepreneurial skills necessary to pursue successful careers in this emerging field of drug discovery. Researchers in the future will require multidisciplinary technological development and knowledge.”
Addressing societal needs
This new generation of researchers will be critical to ensuring that Europe is equipped to address some pressing societal concerns. “We face the problem of an ageing society,” says Pericàs. “New therapies will be needed to treat various diseases of high prevalence, such as Hepatitis B.” On the research side, the scientific discoveries made through VIRO-FLOW could open the door to the more efficient production of new anti-viral compounds in the future. “We hope that the active compounds we found will go on to become novel HBV curative drugs,” says Pericàs. “We envisage that the technologies we used during this project will not only be useful in academic research, but also for industry. The aim is to achieve a more efficient and productive drug discovery process."
