Sunday, May 11, 2025 5/11/2025

Cellular Mechanism of Oxysterol-Binding Protein (OSBP) in Viral Proliferation: A Chemical Biology Approach

Award Number: R01AI154274
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Description

Cellular Mechanism of Oxysterol-Binding Protein (OSBP) in Viral Proliferation: A Chemical Biology Approach - The current COVID-19 crisis starkly illustrates the need to develop new modalities for the therapeutic treatment of pathogenic single-stranded RNA (ssRNA) viruses, including against novel viruses that have yet to emerge. Human oxysterol-binding protein (OSBP) has recently been determined to be a critical mediator in the replication of a broad spectrum of ssRNA viral human pathogens, including the enteroviruses, rhinovirus, hepatitis C, Zika virus, Dengue fever viruses, and coronaviruses. OSBP is an ER-located, non-enzymatic protein reported to function as an important lipid sensor and lipid transporter in eukaryotic cells. Published research, including our own recent publications, has established the antiviral activity of structurally-diverse OSBP- targeting small molecules against multiple RNA pathogenic viruses. These discoveries present the opportunity for a paradigm shift in antiviral drug development: potentially drug targeting a human host protein, OSBP, that is required for viral proliferation of a broad-spectrum of RNA viruses, as opposed to targeting viral proteins present in individual viruses. We have discovered that transient, low dose treatment with the OSBP-targeting compound OSW-1-compound induces a longterm, multigenerational repression of OSBP, and the cells with repressed OSBP show a pronounced inhibition of ssRNA viral replication. Our preliminary results show that the OSW-1- compound has prophylactic antiviral activity at low nanomolar concentrations against several ssRNA viruses, including against one coronavirus tested. The longterm repression of OSBP, triggered by OSW-1, has no effect on cellular division, viability, or morphology. The purpose of this proposal is to understand the cellular role of OSBP in innate antiviral response. Our preliminary results show that OSBP: 1) regulates mTORC1 activity, 2) induces autophagy; 3) slows global protein translation; and 4) activates alternative splicing nonsense- mediated decay (AS-NMD) process, which is an RNA regulatory process. All of these OSBP- involved cellular processes would limit ssRNA viral replication individually, but there is little insight into the organization of these systems to establish a coordinated antiviral response.Our overall hypothesis is that OSBP serves in a major regulatory role to coordinate a multifaceted innate antiviral response to ssRNA infection. We propose a complete model of how OSBP senses early- stage viral infection and then triggers a multisystem response to block viral replication in cells, including through modulating mTOR1C activity and the AS-NMD system.


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 = $390,514 )
2025	2025	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	5	4/11/2025	NON-COMPETING CONTINUATION	$390,514
														Subtotal = $390,514

Issue Date FY: 2024 ( Subtotal = $415,180 )
2024	2024	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	4	3/20/2024	NON-COMPETING CONTINUATION	$397,764
2024	2024	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	001	4	3/21/2024	SUPPLEMENT FOR EXPANSION	$17,416
														Subtotal = $415,180

Issue Date FY: 2023 ( Subtotal = $467,731 )
2023	2023	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	002	3	5/16/2023	SUPPLEMENT FOR EXPANSION	$33,183
2023	2023	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	001	3	3/16/2023	NON-COMPETING CONTINUATION	$399,717
2023	2023	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	2	12/22/2022	SUPPLEMENT FOR EXPANSION	$34,831
														Subtotal = $467,731

Issue Date FY: 2022 ( Subtotal = $397,762 )
2022	2022	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	2	3/8/2022	NON-COMPETING CONTINUATION	$397,762
														Subtotal = $397,762

Issue Date FY: 2021 ( Subtotal = $416,909 )
2021	2021	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	1	4/8/2021	NEW	$416,909
														Subtotal = $416,909

Grand Total All Awards = $2,088,096

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Cellular Mechanism of Oxysterol-Binding Protein (OSBP) in Viral Proliferation: A Chemical Biology Approach

Award Number: R01AI154274

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer