# Innate Immune Regulation of the Epithelium in Chronic Rhinosinusitis with Nasal Polyps

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $141,446

## Abstract

ABSTRACT
The ongoing outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major threat to global health.
The nasal passages are the key portal of entry for airway virus infections, and evidence
suggests that the nasal epithelium is a key reservoir for SARS-CoV-2 and a source of viral
shedding that accounts for high transmissibility and elevated rates of COVID-19. We
hypothesize that diminished interferon-induced innate immune responses in infected nasal
epithelial cells is a primary mechanism allowing rapid viral replication without cytotoxicity. The
parent grant focuses on how human sinonasal epithelial cell populations participate in immune
defense and damage repair. In this supplement proposal, in response to NOT-AI-20-031, we
will extend these studies to research in depth the epithelial cell innate immune response to
SARS-CoV-2. Specifically, delayed interferon signaling may prevent induction of nitric oxide,
which has been previously shown to inhibit viral entry and replication. Nitric oxide can be
induced in nasal epithelial by stimuli other than interferon, including through activation of bitter
taste receptors expressed on the cilia. There are a number of approved medications in clinical
use that taste bitter and can bind to bitter taste receptors. Among these, certain anti-nausea
and antihistamines are particularly strong bitter taste agonists. In this proposal, we will test the
ability of these medications to inhibit SARS-CoV-2 infection of primary nasal epithelial cells in
vitro. We will then use pharmacologic modulators of the bitter taste signaling and nitric oxide
pathways to establish the mechanism of action of drugs that decrease infection. We will also
determine if these medications impact the interferon response to SARS-CoV-2 infection. If
successful, these studies may lay the foundation for novel therapeutic approaches to enhance
the initial epithelial cell innate immune defense against SARS-CoV-2 infection, limiting
progression of COVID-19 and decreasing transmissibility.

## Key facts

- **NIH application ID:** 10187233
- **Project number:** 3R01AI132590-03S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ANDREW P LANE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $141,446
- **Award type:** 3
- **Project period:** 2020-07-16 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10187233

## Citation

> US National Institutes of Health, RePORTER application 10187233, Innate Immune Regulation of the Epithelium in Chronic Rhinosinusitis with Nasal Polyps (3R01AI132590-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10187233. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*