# Defining the viral PTMome: Towards the development of novel antiviral approaches

> **NIH NIH DP1** · CLEVELAND CLINIC LERNER COM-CWRU · 2022 · $1,127,000

## Abstract

PROJECT SUMMARY
 Over the past several decades, the traditional approach to combating viral infectious
diseases has been to target the virus itself, in most cases by either blocking virus-encoded
enzymes that are required for viral replication, or by preventing the virus from entering host cells.
One of the major caveats of these approaches has been the ability of the virus to readily mutate
and thereby become resistant to these classical types of antiviral therapies. In fact, this is a
serious problem for the therapy of RNA virus infections, such as HIV or influenza virus, which are
known to rapidly mutate and thereby escape antiviral drugs. Additionally, traditional antiviral
approaches are designed to target a specific virus, and therefore are ineffective against any new
virus that may emerge in the future, and it is impossible to predict what virus will cause the next
outbreak or pandemic. Therefore, there is the urgent need to develop new ways for targeting viral
pathogens, which will require creative and innovative research.
 Like human proteins, viral proteins robustly undergo posttranslational modifications
(PTMs) for their regulation and proper functioning in the virus life cycle. In most cases, viral PTMs
are dynamically regulated by human enzymes, such as kinases/phosphatases, ubiquitin E3
ligases/deubiquitinating enzymes, or acetyl transferases/deacetylases. Thus, cellular enzymes
play an important role in controlling the ability of the virus to replicate and to cause disease.
 This proposal’s overarching goal is to comprehensively map the ‘viral PTMome’ to identify
the PTMs that are essential for virus replication and pathogenesis. We will combine proteomics
screens and molecular virology approaches including reverse genetics techniques with cutting-
edge molecular, biochemical and biophysical studies. This will allow us to identify and
characterize viral PTMs and the responsible host modifying enzymes, as well as to determine
their roles for effective viral replication and pathogenesis. This powerful approach, combined with
collaborative studies to design and test chemical inhibitors to block the enzymes that regulate
critical viral PTMs, will not only provide unique mechanistic insight into host control of virus
replication but will also lay the groundwork for developing new antivirals for a range of emerging
viral infectious diseases.

## Key facts

- **NIH application ID:** 10490866
- **Project number:** 5DP1AI169444-02
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Michaela Ulrike Gack
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,127,000
- **Award type:** 5
- **Project period:** 2021-09-30 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10490866

## Citation

> US National Institutes of Health, RePORTER application 10490866, Defining the viral PTMome: Towards the development of novel antiviral approaches (5DP1AI169444-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10490866. Licensed CC0.

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