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Cell-based viral helicase assay for dengue drug discovery

Award Number: R43AI140867
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: 07/01/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2021

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Cell-based viral helicase assay for dengue drug discovery - SUMMARY The dengue virus (DENV) is a mosquito-borne RNA virus that is responsible for over 390 million infections a year. While dengue fever is mostly self-limiting, severe dengue diseases are the leading causes of hospitalization and death in children living in limited resource areas. Currently, there are no antiviral treatments for dengue diseases and existing vaccines have questionable safety profiles. Due to its global prevalence and economic burden, the discovery of anti-dengue therapeutics is an urgent health priority. The DENV virus encodes nonstructural 3 (NS3), an enzymatic protein with helicase activity. Mutations in NS3's helicase active site prevents viral RNA synthesis initiation and render the virus replication-incompetent. Further, amino acid residues responsible for NS3's helicase activity are conserved across the DENV serotypes. Thus, NS3 is thought to be an attractive target for dengue drug discovery. However, hits identified from biochemical screens suffer from poor in vivo pharmacokinetics issues while hits identified from phenotypic screens are often non-specific. Therefore, a HTS assay that can specifically target NS3 helicase activity and be performed in cell-based formats would enable the identification of more pharmacoactive hits. This Phase I SBIR application aims to develop a genetically encodable fluorescent sensor that can report small molecule modulations of helicase activities and a proof-of-concept cell-based assay that can identify small molecules that inhibit NS3 helicase activity in vivo. We believe the eventual cell-based HTS platform would be a highly valuable tool in dengue drug discovery.


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: 2022 ( Subtotal = $0 )
2022	2018	LUCERNA INC	760 PARKSIDE AVE	BROOKLYN	NY	11226	KINGS	USA	Allergy and Infectious Diseases Research	000	1	1/28/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	LUCERNA INC.	760 PARKSIDE AVE STE 311	BROOKLYN	NY	11226	KINGS	USA	Allergy and Infectious Diseases Research	000	1	8/7/2020	NEW	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $224,475 )
2018	2018	LUCERNA INC.	760 PARKSIDE AVE STE 311	BROOKLYN	NY	11226	KINGS	USA	Allergy and Infectious Diseases Research	001	1	9/7/2018	NEW	$0
2018	2018	LUCERNA INC.	760 PARKSIDE AVE STE 311	BROOKLYN	NY	11226	KINGS	USA	Allergy and Infectious Diseases Research	000	1	5/10/2018	NEW	$224,475
														Subtotal = $224,475

Grand Total All Awards = $224,475

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Cell-based viral helicase assay for dengue drug discovery

Award Number: R43AI140867

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: 07/01/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2021

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