Exploring the role of antiviral drugs before and after eradication
This area of research involves the development of antiviral treatments to minimize the risk to eradication posed by immune deficient poliovirus excretors, and protect the polio-free free world after eradication.
There are three anticipated situations for the use of polio antiviral drugs:
- treatment of immunodeficient people who are excreting poliovirus;
- preventative treatment for people exposed to poliovirus, for example through unintentional laboratory exposure;
- use in communities exposed to circulating vaccine-derived poliovirus (cVDPV) outbreaks in the post-eradication era (likely in conjunction with inactivated polio vaccine).
In 2006, the Poliovirus Antivirals Initiative was established. Its immediate goal was to determine if candidate antiviral drugs were safe and able to prevent, reduce or stop poliovirus shedding in immune deficient adults given the oral polio vaccine.
Multiple drug candidates were screened, including capsid inhibitors and protease inhibitors, and popocavir was identified as the lead candidate. Pocapavir has been tested in a clinical study with adults, confirming that treatment is safe and significantly accelerated virus clearance. However, emergence of resistance and virus transmission were seen in the context of a clinical isolation facility. Currently, the Poliovirus Antivirals Initiative is developing a combination pocapavir and another candidate (V-7404) working by a different mechanism – protease inhibition – in order to reduce the potential for the emergence of resistance.