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

> **NIH NIH P20** · UNIVERSITY OF KANSAS LAWRENCE · 2021 · $209,821

## Abstract

PROJECT SUMMARY
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. Main protease (Mpro)
encoded by SARS-CoV-2 processes the viral polyproteins and facilitates viral replication. Once activated, this
enzyme can evade the host innate immune responses by cleaving host proteins. The host protein substrates of
SARS-CoV-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 the specificity and sensitivity of the 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 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 which host pathways are altered by this SARS-CoV-2 to cause a severe disease condition.
Moreover, host targets of MPro can be used to develop treatment regimens to treat severe cases if 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.

## Key facts

- **NIH application ID:** 10270505
- **Project number:** 2P20GM113117-06
- **Recipient organization:** UNIVERSITY OF KANSAS LAWRENCE
- **Principal Investigator:** Ronak R Tilvawala
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $209,821
- **Award type:** 2
- **Project period:** 2016-05-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10270505

## Citation

> US National Institutes of Health, RePORTER application 10270505, Host Substrate Profiling of SARS-CoV-2 Virus Protease (2P20GM113117-06). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10270505. Licensed CC0.

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