Poliovirus antiviral drugs offer the only mitigation of these risks.  Efforts to discover and develop poliovirus antiviral agents have been ongoing since the formation in 2007 of the Poliovirus Antivirals Initiative (PAI). PAI is a collaborative project among the Bill & Melinda Gates Foundation, the World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC), National Institutes of Health, Rotary International, the Food and Drug Administration, and the Jeffrey Modell Foundation. The Task Force serves as the PAI secretariat.

Two antivirals working by different mechanisms of action are currently under development by ViroDefense Inc.. The development work is funded by the Bill & Melinda Gates Foundation. The most advanced antiviral, pocapavir (V-073), is a capsid inhibitor that has demonstrated activity in an oral poliovirus vaccine human challenge model and in the compassionate use treatment of immune deficient iVDPV excreters. The second antiviral, V-7404, is a virus specific protease inhibitor that is presently being studied in a Phase 1 clinical study. The goal is to have two antivirals available for use in combination to treat iVDPV to increase efficacy and reduce the potential for drug resistance to develop. In addition to antiviral development, PAI is also working with PATH to develop a point of care diagnostic that will help identify immune deficient people.