# MiRNA-based Therapeutics for SARS-CoV-2 S1 mediated neuroinflammation and beta-amyloid production

> **NIH NIH R03** · UNIVERSITY OF SOUTH FLORIDA · 2022 · $74,750

## Abstract

Project summary/Abstract
There is ample evidence that SARS-CoV-2, the causative agent of COVID-19, causes
neurological symptoms but there is insufficient evidence that the virus can directly infect the brain.
It has been suggested that neurological symptoms might be due to additional factors such as
cytokine storm, neuroimmune stimulation, and systemic SARS-CoV-2 infection, rather than by
direct CNS damage caused by the virus. The S protein is the main antigenic component of SARS-
CoV-2 structural protein and its proteolytic processing allows the S1 subunit to dissociate, which
then triggers the S2 subunit rearrangement that is required for fusion. Also, TLR4 is the most
important member of the TLR family for pathogen recognition and helps to provide first line
defense against infections through inflammatory factors induction. Herein, we propose to test the
hypothesis that the cleaved S1 subunit itself enters the brain parenchyma causing
neuroinflammation and b-amyloid accumulation and TLR4-targeted microRNA(s) can inhibit these
processes. This hypothesis will be tested in two specific aims. First,
we will test if S1 directly
interacts with TLR4 in microglia and initiates immune responses that leads to excessive activation
of the pathway, which disrupts immune homeostasis and results in chronic brain inflammation
and b-amyloid accumulation. Second, we will test the role of specific miRNAs, selected using
bioinformatics prediction tools, in regulating the S1-initiated neuroinflammation. After
experimental validation of miRNA targets, specific miRNAs will be enriched in exosomes and
tested for their ability to end the positive feedback loop between inflammation and b-amyloid
production. The results are expected to provide mechanistic insights into the COVID-19 effects
on neuroinflammation and dementia and lead to the development of miRNA therapeutics against
covid-induced regulatory loop between inflammation and b-amyloid production.

## Key facts

- **NIH application ID:** 10433303
- **Project number:** 1R03NS127075-01
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Eleni Markoutsa
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $74,750
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10433303

## Citation

> US National Institutes of Health, RePORTER application 10433303, MiRNA-based Therapeutics for SARS-CoV-2 S1 mediated neuroinflammation and beta-amyloid production (1R03NS127075-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10433303. Licensed CC0.

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