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BROAD-SPECTRUM, SMALL-MOLECULE INHIBITORS OF BUNYAVIRUSES

Award Number: U01AI082108
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/23/2009
PERIOD OF PERFORMANCE END DATE: 08/31/2011

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BROAD-SPECTRUM, SMALL-MOLECULE INHIBITORS OF BUNYAVIRUSES - DESCRIPTION (provided by applicant): The family Bunyaviridae is comprised of a diverse group of viruses spread across five genera and infecting hosts from both the plant and animal kingdoms. Significant biothreats among these are several human pathogens including Rift Valley fever virus (RVFV), Crimean-Congo hemorrhagic fever virus (CCHF), hantavirus, and La Crosse encephalitis virus (LACV). A broad-spectrum bunyavirus antiviral would have great utility against natural or intentional introduction of these agents into population centers, as well as provide a treatment option in areas where these pathogens are endemic. The goal of the SIGA Bunyavirus product development program described here is to develop a broad-spectrum, small-molecule therapeutic for the treatment and prevention of disease caused by RVFV, a Category A priority pathogen, and LACV, a ategory B pathogen. Using sensitive high-throughput screens developed for both LACV and RVFV, we have identified several candidate compounds (quality hits) with broad-spectrum antiviral properties against these related pathogens from among the 206,000 small molecules in the SIGA chemical compound library. This dual screening strategy has also allowed identification of nontoxic compounds with antiviral activities that extend beyond the family Bunyaviridae against viruses in the Poxviridae, Togaviridae, and Flaviviridae families, presumably by targeting host pathways essential for replication of a diversity of virus families. Lead series will be assessed with respect to mechanism of action, metabolic stability, pharmacokinetic properties, and efficacy in small animal models of bunyavirus disease in an effort to obtain data necessary for the submission of an application for an Investigational New Drug (IND). RELEVANCE (See instructions): To date, there are no specific vaccines or antivirals approved for the treatment of the Category A, B, or C bunyavirus infections in humans.Of note is the presence of four different members of the family Bunyaviridae among the viruses characterized as biothreats to the United States. The development of a broad-spectrum antiviral treatment for bunyavirus infection is the primary goal of the work outlined in this proposal.


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: 2010 ( Subtotal = $492,578 )
2010	2010	SIGA TECHNOLOGIES, INC	420 LEXINGTON AVENUE	NEW YORK	NY	10170	NEW YORK	USA	Trans-NIH Recovery Act Research Support	000	2	8/30/2010	NON-COMPETING CONTINUATION	$492,578
														Subtotal = $492,578

Issue Date FY: 2009 ( Subtotal = $1,174,957 )
2009	2009	SIGA TECHNOLOGIES, INC	420 LEXINGTON AVENUE	NEW YORK	NY	10170	NEW YORK	USA	Trans-NIH Recovery Act Research Support	000	1	9/18/2009	NEW	$1,174,957
														Subtotal = $1,174,957

Grand Total All Awards = $1,667,535

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BROAD-SPECTRUM, SMALL-MOLECULE INHIBITORS OF BUNYAVIRUSES

Award Number: U01AI082108

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/23/2009

PERIOD OF PERFORMANCE END DATE: 08/31/2011

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