# Development of fluorogenic and chemiluminogenic main protease substrates for cellular and in vivo imaging of SARS-CoV-2

> **NIH NIH R21** · TEXAS A&M UNIVERSITY · 2022 · $224,580

## Abstract

PROJECT SUMMARY
 COVID-19 is the currently prevailing pandemic that has paralyzed much of the world. The viral pathogen of
COVID-19 is SARS-CoV-2, a coronavirus with a positive sense RNA genome. Its production in the human cell
host requires the activity of its main protease (MPro). As a unique enzyme that is essential to SARS-CoV-2, MPro
is acutely toxic to the host cell indicating that it is tightly regulated during viral infection and replication. Its activity
also represents active viral reproduction in organs and tissues in an infected host organism. Therefore, the
detection of MPro activity in SARS-CoV-2-infected cells and animals will provide essential information about MPro
activity regulation in the host cell and SARS-CoV-2 spreading and distribution in a host organism respectively
for the elucidation of SARS-CoV-2 replication and pathogenesis. Noninvasive imaging reagents will be critical
for the detection of MPro activity in order to avoid interference with both the virus and the host. With an ultimate
goal of understanding the SARS-CoV-2 replication in infected cells and elucidating SARS-CoV-2 spreading
patterns and organ/tissue distribution in infected animals, the current proposal aims to develop noninvasive
fluorogenic and chemiluminogenic MPro substrates that have highly cellular stability and tissue penetrability for
imaging MPro activity. Three specific aims will be pursued by 1) developing fluorogenic and chemiluminogenic
MPro substrates; 2) characterizing fluorogenic and chemiluminogenic MPro substrates on their selectivity, cellular
stability and tissue penetrability; and 3) conducting cellular and in vivo imaging of SARS-CoV-2 infection. The
successful completion of the proposed study will 1) result in fluorogenic and chemiluminogenic MPro substrates
with optimal cellular stability and tissue penetratability that can be broadly adopted by COVID-19 researchers for
the investigation of SARS-CoV-2 replication and pathogenesis and 2) provide critical information for the
elucidation of Mpro activity regulation in SARS-CoV-2-infected cells and SARS-CoV-2 spreading patterns and
distribution in transgenic hACE2+ mice.

## Key facts

- **NIH application ID:** 10432895
- **Project number:** 1R21EB032983-01
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** Wenshe Ray Liu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $224,580
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10432895

## Citation

> US National Institutes of Health, RePORTER application 10432895, Development of fluorogenic and chemiluminogenic main protease substrates for cellular and in vivo imaging of SARS-CoV-2 (1R21EB032983-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10432895. Licensed CC0.

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