# Core C: Enzymology Core

> **NIH NIH U19** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $7,462,555

## Abstract

ABSTRACT
The overarching goal of Core C is to support READDI-AC discovery efforts in collaboration with Discovery Core
B and MedChem Core D by validation, characterization, and optimization of compounds in enzyme assays and
structural studies, and to provide the Research Projects with detailed mechanisms of action and mechanistic
insights to mitigate potential problems with resistance conferring mutations.
Enzymology Core C includes seven internationally recognized laboratories that cover complementary expertise
at the interfaces of virology, biochemistry, biophysics and structural biology. Three specific aims that describe
the central activities of Enzymology Core C:
Aim 1: Develop assays to support hit discovery efforts by Discovery Core B.
Key activities include the expression and purification of enzymes that the Research Projects and Discovery
Core B have selected as targets. Enzymology Core C will support the development of protocols for the
expression and purification of new enzyme targets and their corresponding assays to monitor activity and
inhibition. The translation of enzyme assays into high density formats to facilitate high throughput screening by
Discovery Core B is a second responsibility.
Aim 2. Structural Biology to guide hit and lead optimization.
Enzymology Core C will focus on solving 3D structures of polymerases and RNA helicases that are currently
not available to the scientific community. Priority will also be given to solving the structures of flavivirus and
alphavirus polymerases in complex with the nucleotide and non-nucleotide analog inhibitors to provide detailed
information on the inhibitor binding sites.
Aim 3. Support the Projects in detailed mechanism of action studies for lead compounds.
Functional assays will be employed to assess the inhibitory activity against the biologically relevant enzyme
target, such as measurements of the half maximal inhibitory concentration to determine compound potency.
Promising hits and leads will also be tested against homologous enzymes within the protein family as well as
distant enzymes to assess breadth and the potential for off-target activity. Enzymology Core C will provide an
array of state-of-the-art biochemical/biophysical approaches to provide MedChem Core D and the Projects with
information on the mechanisms associated with inhibition and resistance.

## Key facts

- **NIH application ID:** 10513682
- **Project number:** 1U19AI171292-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** CRAIG E. CAMERON
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $7,462,555
- **Award type:** 1
- **Project period:** 2022-05-16 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10513682

## Citation

> US National Institutes of Health, RePORTER application 10513682, Core C: Enzymology Core (1U19AI171292-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10513682. Licensed CC0.

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