Leading the fight against neglected and emerging viruses
EU-funded researchers have developed a streamlined approach for identifying and testing antiviral compounds that promises to accelerate the search for treatments for a range of deadly diseases including Ebola, SARS and dengue fever. Negotiations are underway for a class of compounds which are nearly ready for the pharmaceutical industry to pursue.
© Giovanni Cancemi - fotolia
In the battle against viral epidemics, such as the recent Ebola outbreak in West Africa or the emergence of Middle East Respiratory Syndrome (MERS) in Saudi Arabia in 2012, time is always of the essence. But until recently a number of diseases caused by viruses – including Ebola – have not been considered suitable targets for drug discovery by the global pharmaceutical industry because it was not deemed commercially viable.
EU funding is helping to fill this void through the SILVER project, which brings together some of Europe and Asia’s leading virologists, molecular biologists, crystallographers, biochemists, medicinal chemists and bioinformaticists.
Over four years, they have screened thousands of molecules, compounds and proprietary drugs for their inhibitory activity against a range of RNA viruses that have either been largely neglected by the pharmaceutical industry, such as human enteroviruses, respiratory viruses, rabies, West Nile encephalitis and dengue haemorrhagic fever, or viruses that are emerging as epidemic threats, such as the SARS and MERS coronaviruses.
SILVER partners have identified a large number of compounds that selectively inhibit the replication of one or more viruses. The activity of the most promising inhibitors was optimised by chemical modification, and proof of concept studies were performed using in vivo model systems.
Additionally, a toolbox of assays (test substances for analysis) was developed to facilitate identification of novel inhibitors of viral replication at low bio-containment levels, thereby reducing costs and improving safety for operators.
The project is negotiating with pharmaceutical companies to test a class of compounds and data packages that includes at least three inhibitors.
“Even if only one finally shows good efficacy in humans, this would be a major achievement,” explains project coordinator Ernest Gould of Aix-Marseille Université in France. Finding effective antiviral compounds faster.
In the case of emerging viruses and epidemic threats, the streamlined, multidisciplinary pipeline approach adopted by the SILVER consortium – from initial screening of inhibitors to proof of concept – significantly accelerates the process of identifying potentially effective antiviral compounds.
Gould notes that the MERS outbreak in the Middle East occurred two years after the SILVER project was launched. By dedicating some of the project’s funds to screening for inhibitors against the emerging respiratory disease, the team was able to identify potential candidates within a matter of weeks.
“Our pipeline strategy was conceived to ensure total integration and automatic progression of all the necessary stages, from compound discovery to proof of concept studies of inhibitors that are ready to be presented to the pharmaceutical industry,” Gould explains. “However, developing drugs from these inhibitors will still require preclinical and clinical studies. This stage of drug development falls outside the scope and mission of the consortium.”
The SILVER team are hopeful that their work will spur the development of new treatments for neglected and emerging viruses – a process that may nonetheless take several years due to the cost and complexity of conducting clinical trials. Nonetheless, the high quality data packages generated by the project provide the pharmaceutical industry with an excellent starting point for further optimisation, preclinical and clinical development and assessment of antiviral compounds.
According to Gould, “The Ebola outbreak has certainly raised global awareness of the problem of emerging diseases that face mankind, but there are many other neglected viruses that cause billions of infections and kill millions of people annually.”
Several of the SILVER project partners are hoping to continue their work in follow-up projects, and may seek funding under the EU’s Horizon 2020 programme.