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 Gates Foundation, the World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC), and the National Institutes of Health. The Task Force serves as the PAI secretariat.

The most advanced program involves two antivirals working by different mechanisms of action under development by ViroDefense Inc. The development work is funded by the Gates Foundation. One 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 vaccine-derived poliovirus (iVDPV) excreters. The second antiviral, imocitrelvir (V-7404), is a virus-specific, irreversible protease inhibitor. The goal is to develop two antivirals 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.