Pocapavir for neonatal enteroviral sepsis: limitations of rapid viral sequencing on treatment decisions

ABSTRACT Background Neonatal enterovirus infection can be severe and life-threatening, and there is ongoing interest in the development of antiviral compounds; however, their clinical efficacy has not been definitively proven. Case Summary We describe a case of neonatal enterovirus infection treated with the investigational therapeutic pocapavir, a viral capsid inhibitor. We describe the medical decision-making regarding the choice to offer pocapavir therapy. Because of clinical uncertainty about whether pocapavir contributed to clinical improvement, we performed sequencing of the viral genome and modeled the pocapavir pocket-binding site for evidence of genetic and protein changes before or after the initiation of pocapavir that might confer antiviral resistance. Conclusion This case and our findings reveal the challenges in interpreting sequence analysis of clinical enterovirus isolates to inform clinical decision-making regarding the use of pocapavir for the treatment of neonatal enterovirus.