# Development of 2C inhibitors as broad-spectrum enterovirus antivirals

> **NIH NIH R01** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $755,280

## Abstract

Project Summary
 Non-polio enteroviruses (NPEVs) are etiological agents for several human diseases including respiratory
infections, hand-foot-and-mouth disease (HFMD), aseptic meningitis, encephalitis, neonatal sepsis,
myocarditis, conjunctivitis, and acute flaccid paralysis. Among the more than 100 serotypes of NPEVs, some of
the most significant pathogens are enterovirus D68 (EV-D68), enterovirus A71 (EV-A71) and coxsackievirus B3
(CV-B3). According to CDC, these NPEVs combined have caused 10 to 15 million infections and tens of
thousands of hospitalizations in the U.S. Clearly, NPEVs are a public concern for both U.S. and the world.
 No vaccines are available in the U.S. for the NPEVs such as EV-D68, EV-A71, and CV-B3. Three
inactivated EV-A71 vaccines are available in China. However, there are not broadly protective, and the efficacy
is limited to certain strains. There is no FDA-approved antiviral for any of these NPEVs. Thus, there is a
pressing need to develop orally bioavailable pan-enterovirus antivirals.
 This proposal focuses on targeting the enterovirus nonstructural 2C protein for the development of orally
bioavailable broad-spectrum NPEV antivirals. Specifically, in Aim 1, we will optimize the antiviral activity and
pharmacokinetic properties of three series of 2C inhibitors. In Aim 2, we will determine the high-resolution X-
ray crystal structures of EV-A71, EV-D68, and CV-B3 2C proteins with structurally disparate 2C inhibitors. In
Aim 3, we will evaluate the in vivo antiviral efficacy of 2C inhibitors in EV-D68 and EV-A71 infection mouse
models. Successful implementation of this proposal will provide orally bioavailable broad-spectrum NPEV drug
candidates for further development.

## Key facts

- **NIH application ID:** 10773353
- **Project number:** 1R01AI179926-01
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** Jun Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $755,280
- **Award type:** 1
- **Project period:** 2023-12-01 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10773353

## Citation

> US National Institutes of Health, RePORTER application 10773353, Development of 2C inhibitors as broad-spectrum enterovirus antivirals (1R01AI179926-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10773353. Licensed CC0.

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