# Biochemical and structural mechanisms at the filoviral-host interface

> **NIH NIH P01** · WASHINGTON UNIVERSITY · 2024 · $1,189,295

## Abstract

RP01 Project Summary/Abstract for Biochemical and structural mechanisms at the filoviral-host
interface
The recent filoviral outbreaks, including the 2013-2016 Ebola virus (EBOV) outbreak in West Africa that
introduced the virus to other continents, highlight the imminent threat to global health posed by filoviruses and
the urgent need for basic and translational efforts. The current COVID-19 pandemic further illustrates the
significance of understanding infectious diseases. While recent efforts to develop countermeasures have
resulted in vaccine candidates and some therapeutics, filoviruses remain a considerable threat to human
health and key questions are still outstanding. There are substantial gaps in our understanding of host-viral
interactions that contribute to disease, including how viral proteins limit host responses and assemble into
infectious particles. Work in Research Project 1 (RP01) will use proteomic, biochemical, and structural
methods to identify and validate molecular mechanisms at the host-viral interface in cellular networks to
address this gap. We will address these longstanding mechanistic questions using biochemical and hybrid
structural methods, including mass spectrometry, NMR, X-ray crystallography, small angle X-ray scattering
(SAXS), and cryoelectron microscopy (cryo-EM), cryoelectron tomography (cryo-TM) to characterize filoviral
nucleocapsid (NC) interactions and to define high impact filoviral-host factor interactions modulating PTMs that
impact the viral replication cycle, viral NC assembly, and egress. Our strong publication record, preliminary
results from ongoing studies, and access to unique facilities and resources support these efforts. We are
uniquely positioned due to our highly productive and collaborative team with complementary expertise and a
prior record of co-authored studies with investigators in RP02, RP03, Core B, and Core C. Our Aims are: Aim
1. Determine the structural basis and dynamics of the filoviral nucleocapsid (NC) and define NC-host
interactions; Aim 2. Develop Protein-protein interaction (PPI) maps that include post-translational modifications
(PTMs) from virally infected cells for EBOV and MARV; and Aim 3. Define the molecular mechanisms for PPIs
that contribute to filoviral infection defined by this project, RP02 and RP03. At the completion, we expect to
define filoviral interaction with host factors that contribute to filoviral infection. Our arsenal of tools from mass
spectrometry, biochemistry, and structural biology, together with work from the Research Projects and
Scientific Cores within the PPG, enable us to clearly define each contribution to filoviral infection and identify
new targets for antivirals.

## Key facts

- **NIH application ID:** 10904618
- **Project number:** 5P01AI120943-07
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Gaya K. Amarasinghe
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,189,295
- **Award type:** 5
- **Project period:** 2016-07-07 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904618

## Citation

> US National Institutes of Health, RePORTER application 10904618, Biochemical and structural mechanisms at the filoviral-host interface (5P01AI120943-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10904618. Licensed CC0.

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