Kan “Dylan” Li, MS
Targeting Enterovirus 2C: FP Assay for Inhibitors and PROTACs
Abstract
Enteroviruses (EVs) like EV-D68 and EV-A71 cause illnesses from mild fevers to severe neurological disorders, yet no FDA-approved antivirals target them. The viral 2C protein, a conserved ATPase-helicase essential for RNA replication, is a promising target. Although some 2C allosteric inhibitors show broad-spectrum activity, none have shown in vivo efficacy, likely due to low potency and poor pharmacokinetics. A major hurdle is the lack of direct binding assays. To address this, we developed a fluorescence polarization (FP) assay using Jun14157, a novel probe with strong binding to 2C proteins from EV-D68, EV-A71, and CVB3. The assay will serve as a useful pharmacological tool, and the success of the FP probe design also provides us valuable guidance for proposing two aims: (1) identify new allosteric 2C inhibitors via virtual screening and FP validation; (2) develop PROTACs to degrade 2C protein. This dual strategy aims to advance broad-spectrum antiviral discovery against EVs.
This award serves as a powerful source of self-motivation. When returning to daily work in the lab, it reminds me that the projects I am pursuing truly matter. Being a PhRMA Foundation fellow strengthens my sense of responsibility and professionalism, and it encourages me to conduct every experiment with dedication and enthusiasm.
