# Development of a novel broad-spectrum inhibitor of non-polio enteroviruses associated with acute flaccid myelitis

> **NIH NIH R43** · MICROBIOTIX, INC · 2020 · $298,481

## Abstract

Development of a novel broad-spectrum inhibitor of non-polio enteroviruses associated
with acute flaccid myelitis
Summary:
Despite the eradication of poliovirus in the US and Europe more than 20 years ago, the number
of cases of childhood paralysis associated with acute flaccid myelitis (AFM) has been increasing
since 2014. This surge correlates with a rise in the number of diagnosed infections of 3 non-polio
enteroviruses (NPEVs): enteroviruses D-68 (EV-D68), A71 (EV-A71) and Coxsackievirus A16
(CV-A16) in children. These 3 viruses are associated with a variety of clinical manifestations,
including non-specific febrile illness, respiratory manifestations, hand-foot-and-mouth disease
(HFMD), encephalitis and paralysis (AFM). NPEVs cause more than 10 million infections
worldwide resulting in thousands of hospital admissions, missed days of work and school every
year in the US alone. Consequently, these infections have significant medical, social and
economic impact. Apart from 2 vaccines marketed locally in China for EV-A71, no approved
vaccines or therapeutics exist to treat or prevent NPEV infections or the development of AFM.
We discovered a novel series of compounds that exhibit selective potent antiviral activity against
a group of enteroviruses (poliovirus, EV-D68 and EV-A71) and several other RNA virus families,
but not DNA viruses. Selection for resistant mutants, focused on enteroviruses, identified 2 amino
acid substitutions within the RNA dependent RNA polymerase of poliovirus that conferred
resistance. Our hypothesis is that these compounds constitute a novel series of RNA polymerase
inhibitors. The main objective of this program is to develop a safe and efficacious broad-spectrum
antiviral small molecule inhibitor of all 3 NPEVs that have been linked to AFM: EV-D68, EV-A71
and CV-A16.

## Key facts

- **NIH application ID:** 10008126
- **Project number:** 1R43AI150001-01A1
- **Recipient organization:** MICROBIOTIX, INC
- **Principal Investigator:** Islam Hussein
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $298,481
- **Award type:** 1
- **Project period:** 2020-09-08 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10008126

## Citation

> US National Institutes of Health, RePORTER application 10008126, Development of a novel broad-spectrum inhibitor of non-polio enteroviruses associated with acute flaccid myelitis (1R43AI150001-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10008126. Licensed CC0.

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