Professor Johan Neyts of the KU Leuven in Belgium was awarded a prestigious European Research Council (ERC) Advanced Grant for his groundbreaking project, titled ANTIVIRMAP (Discovery of druggable antiviral targets and replication mechanisms across viral families through chemical probing).
“Viruses, known or yet to emerge, will always remain a health threat,” says Johan Neyts. “Vaccines prevent infections and antiviral drugs are needed for treatment. For most viral infections, however, such drugs do not exist nor are even on the horizon. There is even little knowledge about the weak spots of most viruses and how to block their replication. With ANTIVIRMAP I want to fundamentally revolutionize the discovery of novel targets that can be exploited to develop antiviral drugs. The rabies virus is one of the viruses I will study. Each year at least sixty thousand people die an agonizing death because of rabies. Once symptoms appear, mortality is 100% certain. This is unacceptable; I want to act.”
Antiviral drugs are used to successfully treat infections such as with HIV and HCV. Yet, for most (life)-threatening and neglected infections, there are no such drugs. This leaves also critical gaps in epidemic and pandemic preparedness. Antiviral drug discovery efforts typically focus on a few known targets (e.g., proteases/polymerases). Yet, the biology of viral replication consists of complex processes (e.g., entry, uncoating, genome replication, assembly, egress, host cell interactions) that should harbor a wealth of undiscovered targets. Thus, a large space of potential druggable biology is entirely ignored. My ambition is to fundamentally revolutionize antiviral target-discovery. Using high-throughput, multiplex, high-content multiparametric phenotypic antiviral screening (>350k molecules) against representative, neglected RNA virus families (rhabdo-, alpha-, and bunyaviruses), we will generate rich multiparametric compound fingerprints.
Advanced Artificial Intelligence models will be used to exploit the full complexity of the data to guide the selection of molecules that inhibit or modulate viral replication and that are to be used as unique chemical probes. These will then be systematically characterized through complementary methodologies, including genetic mapping, structural modelling and biochemical validation to obtain detailed understanding of their molecular mechanism of action. The outcome will be a first-of-its-kind “Atlas of Druggable Antiviral Targets”, a multidimensional annotation of druggable viral and host targets. Our efforts will expand the antiviral target space, provide new, much needed starting points for (later) target-based drug discovery and hit-to-lead optimization, deepen our understanding of viral replication biology, establish methodologies broadly applicable to other pathogens and ultimately strengthen preparedness against existing and future viral threats.
ERC Advanced Grants are awarded to individual researchers for a five-year period and are awarded to fundamental, ground-breaking research on the basis of one single criterion: excellence.
Read more about ANTIVIRMAP
