Developing broad-spectrum antiviral drugs for pandemic preparedness.
The threat of virus epidemics continues to increase at an alarming rate. Across recent decades, a range of RNA virus pathogens has emerged from wildlife, or has re-emerged. Pathogens with pandemic potential, like SARS-coronavirus-2, can have worldwide impact by affecting personal and public health, and disrupting the economy and society. This threat is increasing due to societal, ecological, and economic factors. An additional complication is the unpredictable evolution of RNA viruses, which are masters at rapidly adapting to changing circumstances. Therefore, we must understand the risks posed by these viruses and take steps to protect our health, economy, and society.
While vaccination can effectively control viral diseases, there will always be a time gap before a vaccine can be produced and distributed. In this context, directly acting antiviral drugs (i.e. drugs targeting conserved and essential functions in virus replication) offer an important but underappreciated possibility for prophylactic and therapeutic intervention. They will allow the immediate treatment of infected patients and may save the lives of those falling critically ill. As they will reduce virus shedding by these early patients, the R0 may be pushed below 1, which would be an essential contribution to efforts to curb an epidemic.
The conserved nature of many of the targets of directly acting antiviral drugs (like the active sites of viral proteases and polymerases) enhances the chance of broad(er)-spectrum activity because these targets are much less subjected to direct immune selection and tend to evolve more slowly due to structure-function constraints. Thus, directly-acting antiviral drugs can be a critical tool to reduce the impact of virus outbreaks in their earliest phase or even to contain them before becoming a more widespread problem.
The PANVIPREP consortium incorporates 14 European partners with complementary expertise in virology, structural biology, medicinal chemistry, pharmacology, and machine-learning approaches. Together, they aim to contribute to antiviral pandemic preparedness by piloting and progressing antiviral drug development, in particular through
- developing and advancing broad(er)-spectrum antiviral compounds targeting five selected RNA virus families with high epidemic or pandemic potential;
- delivering novel RNA virus knowledge and tools, including molecules that block novel molecular targets in the viral replication cycle;
- implementing technological innovations to accelerate antiviral drug discovery and development.
