# Regulation of inflammatory gene expression during SARS2 infection

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $747,848

## Abstract

PROJECT SUMMARY
Infection causes inflammation, which contributes to pathogen clearance and survival of the host
organism. However, failure to regulate the inflammatory response can often lead to multiple organ
damage and lethality for the host. In the current COVID-19 pandemic caused by the severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2), patients with elevated cytokine levels are
often associated with severe symptoms and mortality. This indicates hyper-activation of specific
inflammatory molecules might be as much a contributing factor to mortality and morbidity as the
virus itself. Thus, there is a dire need to better understand the gene activation dynamics upon
infection and develop therapies to manage the inflammatory response. In 2016 we have shown
that epigenetic inhibition of factors controlling chromatin remodeling of inflammatory genes, like
Topoisomerase 1, can reduce inflammatory gene expression and rescue lethality during bacterial
and viral infection, suggesting that these effects may be applicable in the setting of COVID-19 as
well. Topoisomerase 1 inhibitors are FDA approved and in the list of WHO essential medicines,
thus their widespread usage and cheap cost can be leverage if they are active against COVID-19
as they are in many other infections. In this proposal, we will characterize the role of Top1 and
epigenetic factors controlling chromatin topology during SARS-CoV-2 infection and will test the
feasibility of use of Top1 inhibitors as drugs for the treatment of COVID-19 in animal models. We
will perform mechanistic and preclinical test using epigenetic inhibitors in comparison with
immune blockers used in clinical trials and the current standard of care (glucocorticoids).

## Key facts

- **NIH application ID:** 10783104
- **Project number:** 5R01AI168130-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Ivan Marazzi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $747,848
- **Award type:** 5
- **Project period:** 2022-02-18 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10783104

## Citation

> US National Institutes of Health, RePORTER application 10783104, Regulation of inflammatory gene expression during SARS2 infection (5R01AI168130-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10783104. Licensed CC0.

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