Rational design of highly potent broad-spectrum enterovirus inhibitors targeting the nonstructural protein 2C

Bauer L, Manganaro R, Zonsics B, Hurdiss DL, Zwaagstra M, Donselaar T, Welter NGE, van Kleef RGDM, Lopez ML, Bevilacqua F, Raman T, Ferla S, Bassetto M, Neyts J, Strating JRPM, Westerink RHS, Brancale A, van Kuppeveld FJM.

PLOS Biology, 2020

Summary:

The Enterovirus group of viruses is a large group of human pathogens such as poliovirus and human rhinovirus.  These viruses can cause health complications and in some cases neurological complications.  Currently antivirals against EV's are not available for therapeutic use.  Compounds targeting the inhibition of 2C were evaluated in this study to determine if they could potentially be used without a potential neurological affect.

The Axion MEA platform (system, plates, and software) was used to record the spontaneous electrical activity of primary rat cortical cultures.  After a baseline recording, the wells were dosed with test compounds or DMSO and acute activity was recorded.  Potential therapeutics were assessed in order to determine if they would cause a potential change in spontaneous firing.