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

Award Number: DP1AI169444
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Defining the viral PTMome: Towards the development of novel antiviral approaches - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $1,127,000 )
2025	2025	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Trans-NIH Research Support	000	5	7/17/2025	NON-COMPETING CONTINUATION	$1,127,000
														Subtotal = $1,127,000

Issue Date FY: 2024 ( Subtotal = $1,127,000 )
2024	2024	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Trans-NIH Research Support	000	4	7/10/2024	NON-COMPETING CONTINUATION	$1,127,000
														Subtotal = $1,127,000

Issue Date FY: 2023 ( Subtotal = $1,127,000 )
2023	2023	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Trans-NIH Research Support	000	3	7/26/2023	NON-COMPETING CONTINUATION	$1,127,000
														Subtotal = $1,127,000

Issue Date FY: 2022 ( Subtotal = $1,127,000 )
2022	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Trans-NIH Research Support	000	2	7/8/2022	NON-COMPETING CONTINUATION	$1,127,000
														Subtotal = $1,127,000

Issue Date FY: 2021 ( Subtotal = $1,127,000 )
2021	2021	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Trans-NIH Research Support	000	1	9/17/2021	NEW	$1,127,000
														Subtotal = $1,127,000

Grand Total All Awards = $5,635,000

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

Award Number: DP1AI169444

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/30/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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