# Antibacterial inhibitors of RnpA

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $704,674

## Abstract

PROJECT ABSTRACT
Targeting novel cellular processes is critical to maintaining a fresh antibiotic development pipeline. In that regard,
we hypothesize that the essential Staphylococcus aureus protein, RnpA, is a unique and druggable antimicrobial
target. We also predict that successful RnpA inhibitor development campaigns will provide new classes of broad
spectrum antibiotics that can be used for the therapeutic intervention of S. aureus, other Gram-positive
organisms and Gram-negative pathogens of immediate and emerging healthcare concern. Accordingly, we have
assembled a multi-disciplinary team of microbiologists, biochemists, chemists, computational and structural
biologists to launch a two-pronged approach to determine whether physiologically promising RnpA inhibitors can
be reasonably achieved. Specifically, we will use a whole cell RnpA inhibitor enrichment assay combined with
a validated enzyme target based approach (Aim 1) and fragment-based screening approach (Aim 2) to arrive at
RnpA inhibitors. A benefit of this program is that it allows integration of structural and computational data for
rational hit optimization regardless of their identification route and will be guided by our recently solved S. aureus
RnpA X-ray crystal structure. While the approaches used are cutting-edge, the true innovation of this project
may reside in the target itself. RnpA forms two holoenzymes, both of which mediate distinct and putatively
independently essential cellular functions, RNA degradation and ptRNA maturation. Consequently, targeting
RnpA potentially allows three routes of identifying therapeutically promising chemical classes of inhibitors and
project success, including those that inhibit the protein's modulation of: 1. mRNA decay, 2. ptRNA processing or
3. Both processes.

## Key facts

- **NIH application ID:** 9913451
- **Project number:** 5R01AI134685-03
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Paul M. Dunman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $704,674
- **Award type:** 5
- **Project period:** 2018-05-07 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9913451

## Citation

> US National Institutes of Health, RePORTER application 9913451, Antibacterial inhibitors of RnpA (5R01AI134685-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9913451. Licensed CC0.

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