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Influenza nucleoprotein interactions

Award Number: SC3GM099559
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/08/2012
PERIOD OF PERFORMANCE END DATE: 12/31/2024

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Influenza nucleoprotein interactions - Influenza virus remains an unmet health issue. Although the virus is controlled with annual vaccines, these exhibit variable efficacy, and slow vaccine production means vaccines are not available during an emerging pandemic. Antivirals can stunt an influenza pandemic, but antivirals become ineffective over time due to selection of resistant viruses. These facts highlight the need to identify novel targets for development of new antiviral therapies to combat emerging influenza, control influenza-related disease, and enhance human health. There is urgent need to discover new molecular targets and produce novel antiviral therapies against influenza virus to prevent an emerging pandemic. Our long-term goal is to discover multiple targets that can be exploited in combination to block influenza viruses. Our objective is to characterize influenza nucleoprotein (NP) interactions essential for influenza RNA expression. NP is an essential component of the functional viral ribonucleoprotein (vRNP), responsible for viral mRNA transcription and RNA genome replication. Recently the FDA approved the first antiviral to target this influenza-virus complex. XOFLUZA is an endonuclease inhibitor targeting influenza PA protein of the vRNP complex and has great promise to inhibit influenza infection rapidly. The activity targeted in this new antiviral was discovered via publicly funded research nearly 40 years ago (Krug, 1981) and exemplifies the importance of our proposed research. Our work is complementary and focuses on the nucleoprotein of the vRNP. Our central hypothesis is that elucidating molecular interactions essential for influenza RNA expression will identify novel antiviral targets. It is reasoned that targeting a highly conserved viral protein is less likely to result in evolution of resistance, particularly when the conserved target is attacked at multiple sites. Once better understood, interactions essential to viral RNA expression will reveal novel ways of preventing an emerging influenza virus pandemic. To test our central hypothesis and attain our overall objective, we will pursue the following specific aims: 1) Characterize influenza nucleoprotein interactions essential for vRNP function and 2) Define influenza nucleoprotein interaction with non- structural protein 1. The proposed research is significant because we will identify multiple antiviral targets within conserved regions of NP, reasoned to be less prone to the development of resistance. The proposed research is innovative because it will identify novel targets to inhibit influenza, possibly including host factors that interact with NP but serve redundant functions for the host. This research will advance knowledge of the physiology of influenza virus and provide fundamental information that can be harnessed to support development of new anti-influenza therapies and enhance human health.


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 = -$5,340 )
2025	2023	UNIVERSITY ENTERPRISES CORPORATION AT CSUSB	5500 UNIVERSITY PKWY	SAN BERNARDINO	CA	92407	SAN BERNARDINO	USA	Biomedical Research and Research Training	000	8	4/14/2025	NON-COMPETING CONTINUATION	-$5,340
														Subtotal = -$5,340

Issue Date FY: 2023 ( Subtotal = $110,250 )
2023	2023	UNIVERSITY ENTERPRISES CORPORATION AT CSUSB	5500 UNIVERSITY PKWY	SAN BERNARDINO	CA	92407	SAN BERNARDINO	USA	Biomedical Research and Research Training	001	8	3/7/2023	NON-COMPETING CONTINUATION	$11,025
2023	2023	UNIVERSITY ENTERPRISES CORPORATION AT CSUSB	5500 UNIVERSITY PKWY	SAN BERNARDINO	CA	92407	SAN BERNARDINO	USA	Biomedical Research and Research Training	000	8	12/8/2022	NON-COMPETING CONTINUATION	$99,225
														Subtotal = $110,250

Issue Date FY: 2022 ( Subtotal = $110,250 )
2022	2022	UNIVERSITY ENTERPRISES CORPORATION AT CSUSB	5500 UNIVERSITY PKWY	SAN BERNARDINO	CA	92407	SAN BERNARDINO	USA	Biomedical Research and Research Training	001	7	6/27/2022	NON-COMPETING CONTINUATION	$11,025
2022	2022	UNIVERSITY ENTERPRISES CORPORATION AT CSUSB	5500 UNIVERSITY PKWY	SAN BERNARDINO	CA	92407	SAN BERNARDINO	USA	Biomedical Research and Research Training	000	7	1/10/2022	NON-COMPETING CONTINUATION	$99,225
														Subtotal = $110,250

Issue Date FY: 2021 ( Subtotal = $110,250 )
2021	2021	UNIVERSITY ENTERPRISES CORPORATION AT CSUSB	5500 UNIVERSITY PKWY	SAN BERNARDINO	CA	92407	SAN BERNARDINO	USA	Biomedical Research and Research Training	000	6	12/22/2020	NON-COMPETING CONTINUATION	$99,225
2021	2021	UNIVERSITY ENTERPRISES CORPORATION AT CSUSB	5500 UNIVERSITY PKWY	SAN BERNARDINO	CA	92407	SAN BERNARDINO	USA	Biomedical Research and Research Training	001	6	2/17/2021	NON-COMPETING CONTINUATION	$11,025
														Subtotal = $110,250

Issue Date FY: 2020 ( Subtotal = $110,250 )
2020	2020	UNIVERSITY ENTERPRISES CORPORATION AT CSUSB	5500 UNIVERSITY PKWY	SAN BERNARDINO	CA	92407	SAN BERNARDINO	USA	Biomedical Research and Research Training	000	5	1/22/2020	COMPETING CONTINUATION	$110,250
														Subtotal = $110,250

Issue Date FY: 2017 ( Subtotal = -$2,761 )
2017	2015	UNIVERSITY ENTERPRISES CORPORATION AT CSUSB	5500 UNIVERSITY PKWY	SAN BERNARDINO	CA	92407	SAN BERNARDINO	USA	Biomedical Research and Research Training	000	4	4/7/2017	NON-COMPETING CONTINUATION	-$2,761
														Subtotal = -$2,761

Issue Date FY: 2015 ( Subtotal = $107,250 )
2015	2015	UNIVERSITY ENTERPRISES CORPORATION AT CSUSB	5500 UNIVERSITY PARKWAY	SAN BERNARDINO	CA	92407	SAN BERNARDINO	USA	Biomedical Research and Research Training	001	4	2/18/2015	NON-COMPETING CONTINUATION	$10,725
2015	2015	UNIVERSITY ENTERPRISES CORPORATION AT CSUSB	5500 UNIVERSITY PARKWAY	SAN BERNARDINO	CA	92407	SAN BERNARDINO	USA	Biomedical Research and Research Training	000	4	12/3/2014	NON-COMPETING CONTINUATION	$96,525
														Subtotal = $107,250

Issue Date FY: 2014 ( Subtotal = $107,250 )
2014	2014	UNIVERSITY ENTERPRISES CORPORATION AT CSUSB	5500 UNIVERSITY PARKWAY	SAN BERNARDINO	CA	92407	SAN BERNARDINO	USA	Biomedical Research and Research Training	000	3	1/23/2014	NON-COMPETING CONTINUATION	$96,525
2014	2014	UNIVERSITY ENTERPRISES CORPORATION AT CSUSB	5500 UNIVERSITY PARKWAY	SAN BERNARDINO	CA	92407	SAN BERNARDINO	USA	Biomedical Research and Research Training	001	3	2/28/2014	NON-COMPETING CONTINUATION	$10,725
														Subtotal = $107,250

Issue Date FY: 2013 ( Subtotal = $103,496 )
2013	2013	THE FOUNDATION FOR CALIFORNIA STATE UNIV-SAN BERNARDINO	5500 UNIVERSITY PARKWAY	SAN BERNARDINO	CA	92407	SAN BERNARDINO	USA	Biomedical Research and Research Training	001	2	6/14/2013	NON-COMPETING CONTINUATION	$6,971
2013	2013	THE FOUNDATION FOR CALIFORNIA STATE UNIV-SAN BERNARDINO	5500 UNIVERSITY PARKWAY	SAN BERNARDINO	CA	92407	SAN BERNARDINO	USA	Biomedical Research and Research Training	000	2	11/23/2012	NON-COMPETING CONTINUATION	$96,525
														Subtotal = $103,496

Issue Date FY: 2012 ( Subtotal = $107,250 )
2012	2012	THE FOUNDATION FOR CALIFORNIA STATE UNIV-SAN BERNARDINO	5500 UNIVERSITY PARKWAY	SAN BERNARDINO	CA	92407	SAN BERNARDINO	USA	Biomedical Research and Research Training	000	1	2/8/2012	NEW	$107,250
														Subtotal = $107,250

Grand Total All Awards = $858,145

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Influenza nucleoprotein interactions

Award Number: SC3GM099559

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/08/2012

PERIOD OF PERFORMANCE END DATE: 12/31/2024

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