# Core E – Structural Biology

> **NIH NIH U19** · EMORY UNIVERSITY · 2022 · $1,699,755

## Abstract

Project Summary – Core E
 There is an urgent need for the development of orally bioavailable antivirals that are safe and highly
efficacious against coronaviruses such as SARS-CoV-2 as well as other RNA viruses with pandemic
potential. The development of effective small-molecule antivirals can be greatly accelerated by a thorough
understanding of their biophysical binding constants, mechanisms of action, and structural basis of binding,
which will be provided by Core E: Protein Expression and Structural Biology. This core will be led by Dr.
Jason McLellan at the University of Texas at Austin, who is an expert in structural virology and the
development of structure-based interventions for viral pathogens. His laboratory has expertise in the
determination of viral protein structures, including the first structure of the respiratory syncytial virus (RSV)
polymerase complex, as well as extensive experience in structure-based design and biophysical
characterization of protein interactions.
 The primary mission of Core E of the Antiviral Countermeasures Development Center (AC/DC) is to
determine X-ray or cryo-EM structures of lead compounds identified by the Research Projects in complex
with their viral protein targets. The resulting atomic-level information will be used to rationally design or
optimize lead compounds in silico, as well as determine molecular mechanisms of action. Core E will also
provide protein expression and purification support to Research Projects that need highly active and
pure proteins for compound validation or novel screening approaches. Additionally, Core E will perform
biophysical binding studies to determine thermodynamic and kinetic binding constants for lead
compounds via isothermal titration calorimetry and surface plasmon resonance. These techniques can be
used to identify candidates that bind directly to the target protein as well as enable compound optimization
aimed at improving specific binding parameters. Collectively, the services provided by Core E will
accelerate the development of orally bioavailable antivirals against SARS-CoV-2 and other RNA viruses
with pandemic potential as well as provide novel insights into the structure, function, and inhibition of
important viral proteins.

## Key facts

- **NIH application ID:** 10513940
- **Project number:** 1U19AI171403-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Jason Scott McLellan
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,699,755
- **Award type:** 1
- **Project period:** 2022-05-16 → 2026-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10513940

## Citation

> US National Institutes of Health, RePORTER application 10513940, Core E – Structural Biology (1U19AI171403-01). Retrieved via AI Analytics 2026-07-26 from https://api.ai-analytics.org/grant/nih/10513940. Licensed CC0.

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