# Complex Odor Recognition of the Main Olfactory Bulb

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $194,375

## Abstract

PROJECT SUMMARY
COVID-19 is a devastating disease caused by the severe acute respiratory syndrome coronavirus clade 2
(SARS-CoV2) that has resulted in 100,442 deaths in the U.S. (May 28th, 2020). Smell loss is a major symptom
for COVID-19 (1-4). In a recent publication we identified TRPM5-expressing cells (microvillous cells (MVCs)
and olfactory sensory neurons (OSNs)) as viral-responding cells in the olfactory epithelium (OE)(5). MVCs are
part of a family of TRPM5-expressing cells found in the airways and the intestine that respond to virus, bacteria
and irritants with a type 2 immune response through IL-25 and release of acetylcholine (6, 7). In preliminary
studies we find that intranasal herpes simplex virus type 1 (HSV-1) infection in mice elicits a dramatic shift in
TRPM5 expression from MVCs to the basal epithelium consistent with activation of stem cells (SCs) for
immune defense, as proposed for chronic inflammation of the OE (8-10)
expression
However,
inflammation
It is unclear whether this increased
and altered location of TRPM5 is an aberrant response, contributing to persistent inflammation.
influenza infection increases TRPM5 expressing cells in the lung, leading to damaging persistent
(11) Here
.
. we hypothesize that SARS-CoV-2 infection of OE upregulates TRPM5
expression, leading to proinflammatory cytokine release, decrease in OSN numbers and activity,
persistent inflammation yet ineffective viral clearance leading to worse COVID-19; whereas addition of
TRPM5 blockers will attenuate cytokine release and viral loads.
We
epithelial
flufenamic
will test this hypothesis with studies of changes in inflammation and olfactory function in human olfactory
cell cultures infected with by inhibition of TRPM5 using the FDA approved drug
acid in two specific aims:
SARS-CoV2
Aim 1. Determine if activation of the TRPM5 transduction cascade in MVCs mediates the inflammatory
response to SARS-CoV-2 viral infection leading to loss of olfactory function.
Aim 2. Determine if TRPM5 expression in the OE promotes SARS-CoV-2 neurotropism, facilitating
nervous system disease.

## Key facts

- **NIH application ID:** 10177313
- **Project number:** 3R01DC000566-31S2
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Diego Restrepo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $194,375
- **Award type:** 3
- **Project period:** 1988-12-12 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177313

## Citation

> US National Institutes of Health, RePORTER application 10177313, Complex Odor Recognition of the Main Olfactory Bulb (3R01DC000566-31S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10177313. Licensed CC0.

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