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HIV-1 Integrase Interactions With Viral RNA And Capsid

Award Number: R21AI203593
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: 08/03/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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HIV-1 Integrase Interactions With Viral RNA And Capsid - PROJECT SUMMARY/ABSTRACT HIV-1 integrase promotes encapsidation of the viral genomic RNA within mature capsid cores, an essential, non- catalytic function that is a validated target for antiretroviral drug development. Allosteric integrase inhibitors disrupt this process, leading to mislocalization of viral RNA outside the core, causing catastrophic defects during reverse transcription after host cell entry. We recently discovered that integrase assembles into an RNA-binding filament that propagates along the inner wall of the viral core. This structure provides a conceptual basis for the non-catalytic functions of integrase and reveals previously unrecognized interactions between integrase and the HIV-1 capsid lattice. In this two-year project, we aim to define the geometric and topological rules that govern the positioning of IN filaments within the conical fullerene CA lattice, refine the IN–CA interface to a resolution sufficient to assign roles to individual amino acid side chains, and map the molecular interfaces that mediate the essential IN-RNA interactions. These studies will provide a structural and mechanistic foundation for the second essential function of HIV-1 IN. The results will inform the rational development of next-generation allosteric IN inhibitors and may uncover general principles of genome encapsidation and maturation applicable to other enveloped RNA viruses.


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 = $150,000 )
2026	2026	THE FRANCIS CRICK INSTITUTE LIMITED	1 MIDLAND ROAD	LONDON				GBR	Allergy and Infectious Diseases Research	000	1	8/3/2026	NEW	$150,000
														Subtotal = $150,000

Grand Total All Awards = $150,000

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HIV-1 Integrase Interactions With Viral RNA And Capsid

Award Number: R21AI203593

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: 08/03/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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