# Host Substrate Profiling of SARS-CoV-2 Virus Protease

> **NIH NIH P20** · UNIVERSITY OF KANSAS LAWRENCE · 2020 · $143,427

## Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the viral pneumonia 
outbreak of coronavirus disease 2019 (COVID-19) causing widespread morbidity and mortality. Currently, 
there are no treatment available for this disease. Main protease (Mpro) encoded by SARS-CoV- 
2 processes the viral polyproteins and facilitate viral replication. Once activated, this enzyme could evade 
the host innate immune responses by cleaving host proteins. As such, the host protein substrates of SARSCoV- 
2 Mpro are not well characterized. The major challenges with the direct detection of host protein 
targets is their low abundance and technical limitations with specificity and sensitivity of current methods. 
Thus, this proposal is designed to develop a more specific and sensitive approach termed N-terminomics to 
discover unique protein fragments that are generated by Mpro during SARS CoV-2 infection. The Specific 
Aims of this proposal are: 1) Development and validation of novel NHS ester probes to identify protease 
fragments generated by SARS-CoV-2 Mpro in cell lysate and 2) Identify and quantify the endogenous 
substrates of SARS-CoV-2 Mpro in infected mammalian cells. The rationale for the proposed research is 
that its success would facilitate a greater understanding of how SARS CoV-2 Mpro protease contributes to 
the severity of COVID-19. Moreover, it will aid in developing treatment regimens for COVID-19. The 
expected outcome of this research is that our approach will be more sensitive and readily adaptable for the 
host substrate profiling of any pathogenic proteases and it will aid in mapping cellular pathways which are 
hijacked by pathogens to invade the host system. The successful execution of the research proposed 
herein is expected to have a significant positive impact in reducing morbidity and mortality caused by 
COVID-19.

## Key facts

- **NIH application ID:** 10267801
- **Project number:** 5P20GM113117-05
- **Recipient organization:** UNIVERSITY OF KANSAS LAWRENCE
- **Principal Investigator:** Ronak R Tilvawala
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $143,427
- **Award type:** 5
- **Project period:** 2020-08-18 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10267801

## Citation

> US National Institutes of Health, RePORTER application 10267801, Host Substrate Profiling of SARS-CoV-2 Virus Protease (5P20GM113117-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10267801. Licensed CC0.

---

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