# Identifying Genetic Regulators and New Models of Wild Type Coronavirus Pathogenesis

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $194,375

## Abstract

ABSTRACT
SARS-CoV, and more recently MERS-CoV, are human coronaviruses that have emerged from
zoonotic populations to infect and cause severe disease in humans. Our understanding of
coronavirus pathogenesis is largely limited to what can be observed in small animal models which
appear to recapitulate the disease seen in humans. The SARS-CoV mouse model relies on a
mouse adapted strain of virus, MA15, as the wild type human isolates replicate in mice but do not
cause appreciable signs of disease. Replication models also fail to capture key aspects of the
human response to infection – respiratory dysfunction, inflammation and other signs of disease.
As such, replication models cannot be used to assess either antiviral therapeutics or vaccine
efficacy. While mouse adapted SARS-CoV infection recapitulates many of the aspects of human
SARS-CoV disease, the virus has six point mutations scattered throughout the genome and was
not generated until years after the end of the SARS epidemic. Passage models run the risk of
altering virus tropism or replication from what occurs in the natural host and require sequencing
and extensive analysis know the location and effect of each mutation. Importantly, coronavirus
passage experiments were recently restricted during the Gain of Function research pause and
could now fall under the HHS P3CO Framework, thus limiting our ability to rapidly identify disease
models for emerging pathogens. Additionally, a passage approach to generating a disease
models is time consuming, something that cannot be afforded in the context of a novel virus
outbreak. By generating a new mouse model of wild type SARS-CoV pathogenesis we will
provide an important tool for the evaluation of the pathogenic potential of emerging zoonotic
coronaviruses as well as a resource for testing novel therapeutics and vaccines. Additionally we
will identify genetic regulators that dictate a pathogenic response to wild type SARS-CoV
infection.

## Key facts

- **NIH application ID:** 10177860
- **Project number:** 5R21AI145372-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Lisa Gralinski
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $194,375
- **Award type:** 5
- **Project period:** 2020-06-02 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177860

## Citation

> US National Institutes of Health, RePORTER application 10177860, Identifying Genetic Regulators and New Models of Wild Type Coronavirus Pathogenesis (5R21AI145372-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10177860. Licensed CC0.

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