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Molecular Mechanisms of Pararubulavirus Entry and Fusion Activation

Award Number: F31AI203004
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Molecular Mechanisms of Pararubulavirus Entry and Fusion Activation - Project Summary Pararubulaviruses are bat-derived, emerging, zoonotic paramyxoviruses capable of spilling over from bats and domestic animals into humans, causing disease. Although these viruses pose a growing threat and are classified as biosafety level-3 (BSL-3) pathogens, the molecular mechanisms that control their entry, receptor usage, and fusion activation remain largely unknown. Viral entry requires coordinated activity between the two surface proteins, the receptor binding protein (RBP) and the fusion protein (F). However, unlike many related paramyxoviruses, the host receptors for pararubulaviruses remain unidentified, and the structural determinants that allow RBP to trigger F have not been explored. Understanding these early events is essential for assessing zoonotic potential and guiding antiviral and/or vaccine development. The overall goal of this project is to define the molecular mechanisms that regulate pararubulavirus entry, fusion activation, and receptor usage. Specific Aim 1 will dissect the functional interplay between RBP and F proteins across pararubulaviruses. Using a dual-split reporter fusion assay, I will quantify fusion driven by homotypic and heterotypic RBP–F pairs across different pararubulaviruses. I will then generate domain-swap chimeras and targeted mutations in the RBP stalk and F head to map conserved structural features required for fusion triggering. These studies will define the molecular surfaces that mediate RBP–F crosstalk and reveal whether pararubulaviruses share a conserved fusion-activation mechanism. Specific Aim 2 will define cellular tropism and identify host receptors for zoonotic pararubulaviruses. I will use a genome-wide CRISPR/Cas9 knockout screen on permissive human cells to identify candidate entry receptors. In parallel, I will profile cell tropism using live recombinant virus and pseudotyped VSV bearing pararubulavirus envelope proteins. Soluble RBP binding and competition assays will test whether viruses share or diverge in receptor usage. Together, these approaches will uncover the molecular determinants of host range and zoonotic spillover. By linking envelope protein interactions (Specific Aim 1) with receptor dependence and tropism (Specific Aim 2), this work will generate the first unified mechanistic framework for pararubulavirus entry. These insights will support the development of diagnostics, antivirals, and preparedness strategies for emerging paramyxoviruses. This work will also provide the comprehensive research training I need to become an independent virologist that specializes in emerging infectious diseases. This research will be supervised by Dr. Benhur Lee and Dr. Jean Lim, both recognized leaders in the field of virology.


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 = $49,714 )
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	001	1	8/10/2026	NEW	$0
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	8/10/2026	NEW	$49,714
														Subtotal = $49,714

Grand Total All Awards = $49,714

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Molecular Mechanisms of Pararubulavirus Entry and Fusion Activation

Award Number: F31AI203004

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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