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Antiviral therapeutics for flavivirus infections

Award Number: R01AI093356
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: 05/03/2011
PERIOD OF PERFORMANCE END DATE: 04/30/2018

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Antiviral therapeutics for flavivirus infections - DESCRIPTION (provided by applicant): There is an urgent need for new antivirals for both treatment and control of dengue virus, given that over 50 million people are infected worldwide with dengue every year, including 500,000 cases of the more severe form of the disease, dengue hemorrhagic fever (DHF) and there are no approved vaccines or antiviral drugs available. Vaccine development is promising but faces several significant challenges including the need to balance protection against all four serotypes of the virus equally in order to avoid antibody-dependent enhancement of infection and risk of DHF. An antiviral drug that inhibits viral replication without increasing the risk for ADE would be extremely valuable for public health by providing a means to control outbreaks, as well as to government stockpiles for biodefense preparedness. The overall goal of the SIGA dengue program is to develop a small molecule therapeutic for the treatment and/or prevention of disease caused by dengue virus. A sensitive and specific high throughput screening (HTS) assay has been developed to evaluate compounds from the SIGA chemical compound library for inhibitory activity against dengue-2 (DEN-2) virus replication. Hits have been identified that are potent (EC50<5uM) and selective (CC50>25uM), with initial structure activity relationship in several series of related compounds. Quality hits were characterized for spectrum of activity, mechanism of action (MOA), preliminary absorption, distribution, metabolism and excretion (ADME) properties, preliminary biopharmaceutical properties, and tolerability. Based on this characterization two lead series were identified that have an optimal biological profile consistent with development of an anti-dengue drug. In this application chemical analogs of selected quality hits will be synthesized to improve the properties of the compounds leading to the nomination of a preclinical candidate which will enter into IND-enabling toxicology.


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: 2019 ( Subtotal = -$488,022 )
2019	2015	SIGA TECHNOLOGIES, INC.	31 E 62ND ST	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	5	11/30/2018	NON-COMPETING CONTINUATION	-$488,022
														Subtotal = -$488,022

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2015	SIGA TECHNOLOGIES, INC.	660 MADISON AVE STE 1700	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	5	4/13/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $1,192,443 )
2015	2015	SIGA TECHNOLOGIES, INC	420 LEXINGTON AVENUE	NEW YORK	NY	10170	NEW YORK	USA	Allergy and Infectious Diseases Research	000	5	5/15/2015	NON-COMPETING CONTINUATION	$1,192,443
														Subtotal = $1,192,443

Issue Date FY: 2014 ( Subtotal = $1,246,033 )
2014	2014	SIGA TECHNOLOGIES, INC	420 LEXINGTON AVENUE	NEW YORK	NY	10170	NEW YORK	USA	Allergy and Infectious Diseases Research	000	4	4/9/2014	NON-COMPETING CONTINUATION	$1,246,033
														Subtotal = $1,246,033

Issue Date FY: 2013 ( Subtotal = $1,152,093 )
2013	2013	SIGA TECHNOLOGIES, INC	420 LEXINGTON AVENUE	NEW YORK	NY	10170	NEW YORK	USA	Allergy and Infectious Diseases Research	000	3	4/22/2013	NON-COMPETING CONTINUATION	$1,103,068
2013	2013	SIGA TECHNOLOGIES, INC	420 LEXINGTON AVENUE	NEW YORK	NY	10170	NEW YORK	USA	Allergy and Infectious Diseases Research	001	3	6/13/2013	NON-COMPETING CONTINUATION	$49,025
														Subtotal = $1,152,093

Issue Date FY: 2012 ( Subtotal = $1,260,044 )
2012	2012	SIGA TECHNOLOGIES, INC	420 LEXINGTON AVENUE	NEW YORK	NY	10170	NEW YORK	USA	Allergy and Infectious Diseases Research	000	2	4/19/2012	NON-COMPETING CONTINUATION	$1,260,044
														Subtotal = $1,260,044

Issue Date FY: 2011 ( Subtotal = $1,442,798 )
2011	2011	SIGA TECHNOLOGIES, INC	420 LEXINGTON AVENUE	NEW YORK	NY	10170	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	5/3/2011	NEW	$1,442,798
														Subtotal = $1,442,798

Grand Total All Awards = $5,805,389

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Antiviral therapeutics for flavivirus infections

Award Number: R01AI093356

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: 05/03/2011

PERIOD OF PERFORMANCE END DATE: 04/30/2018

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