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Inhibitors of Non-Structural Protein 2 (nsP2) Protease as Therapeutics Against Venezuelan Equine Encephalitis Virus

Award Number: R01AI201261
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: 08/18/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

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Inhibitors of Non-Structural Protein 2 (nsP2) Protease as Therapeutics Against Venezuelan Equine Encephalitis Virus - Project Summary Emerging viral infections caused by mosquito-borne alphaviruses are looming threats to public health systems. No vaccines or therapeutics are approved for human use against alphaviruses if regional or transnational outbreaks of alphavirus infections occur in the future. Loss of life and economic hardship can be minimized or prevented if therapeutic or prophylactic agents are avail- able. In this research project, we focus on investigating a series of molecules that inhibit the pro- tease domain of the non-structural protein 2 of VEEV, block the replication of VEEV in cell cultures and protect mice against VEEV, and are amenable to systematic structural changes essential for drug development. The overarching goal of this project is to advance new small molecule inhibi- tors of nsp2 and alphaviruses into preclinical development. The specific aims of this project are a). Improve potency of lead candidates through structure-activity relationship studies guided by nsp2 inhibition, in vitro antiviral and ADME assays, pharmacokinetics, tolerability, and efficacy studies in mouse models; and (b). Investigate the ability of the compounds to protect the blood- brain barrier during VEEV infection using an organ-on-the-chip model of the BBB in longitudinal studies. The project goals will facilitate advancing the compound series toward clinical investiga- tions as first-in-class nsP2 protease inhibitors against VEEV. The molecules will also serve as valuable molecular tools to advance our understanding of the role of non-structural protein 2 in the pathogenicity of alphaviruses.


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: 2026 ( Subtotal = $747,400 )
2026	2026	THE UNIVERSITY OF ALABAMA IN HUNTSVILLE	301 SPARKMAN DR NW	HUNTSVILLE	AL	35805	MADISON	USA	Allergy and Infectious Diseases Research	000	1	8/18/2026	NEW	$747,400
														Subtotal = $747,400

Grand Total All Awards = $747,400

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Inhibitors of Non-Structural Protein 2 (nsP2) Protease as Therapeutics Against Venezuelan Equine Encephalitis Virus

Award Number: R01AI201261

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: 08/18/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

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