# Structural and Functional Characterization of the Ebola Virus Replication Complex

> **NIH NIH P01** · WASHINGTON UNIVERSITY · 2020 · $2,554,916

## Abstract

Abstract: Project Overview for Structural and Functional Studies of Ebola Virus RNA synthesis
Ebolaviruses (EBOVs) are non-segmented negative-strand RNA viruses (NNSVs) and Category A Priority
biodefense pathogens that cause frequent lethal hemorrhagic fever, including the devastating and ongoing
outbreak in West Africa. Approved anti-EBOV therapeutics are lacking. EBOV replicates with high efficiency in
vivo while effectively evading host innate antiviral immunity. The unrestrained replication and associated
inflammation leads to death. A complete understanding of EBOV pathogenesis therefore requires
understanding how the viral RNA dependent RNA polymerase (RDRP) complex interacts with host factors.
The overarching goal of this program project proposal is to understand the mechanisms of RDRP function by
defining the interactions among its components and with the host proteome and by defining signals that
regulate its function. Toward this goal Project 1 will identify cis- and trans-acting factors that impact EBOV
RDRP activity. Project 2 will define a structural basis for the EBOV RDRP complex, identify regulatory
mechanisms, and determine species and strain specificities, and Project 3 will use genome-wide RNAi and
proteomic strategies to identify host factors that modulate RDRP function. Project 1 provides functional context
into which a subset of Project 3 “hits” can be interpreted, while Project 3 will likely identify host factors relevant
to the findings of Project 1. Project 2 will provide a structural framework that will be used to integrate findings
from both Projects 1 and 3. Together, these studies will provide mechanistic insights into how protein-protein
and protein-vRNA interactions control EBOV RDRP function. Research projects are supported by an
Administrative Core, a Protein Production and Protein Interaction Core, and critically, a Biosafety Level 4
(BSL4) Core. Core B will generate unique reagents, including monoclonal and synthetic antibodies. Core C
(BSL4) will provide unique capabilities to obtain materials from and perform tests using wild type and mutant
EBOVs as well as pathogenesis evaluation. The work will be performed by highly productive and collaborative
investigators with expertise in every aspect of the proposed studies, including biochemistry, EBOV
pathogenesis, high throughput screening and data analysis, immunology, proteomics, structural biology, and
virology. These studies will provide unprecedented insights into the components of the EBOV RDRP and in its
interaction with the host as well as species and strain differences that affect the RDRP complex. We also
expect to identify specific viral and host factor interactions as novel therapeutic targets.

## Key facts

- **NIH application ID:** 9955168
- **Project number:** 5P01AI120943-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Gaya K. Amarasinghe
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,554,916
- **Award type:** 5
- **Project period:** 2016-07-07 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9955168

## Citation

> US National Institutes of Health, RePORTER application 9955168, Structural and Functional Characterization of the Ebola Virus Replication Complex (5P01AI120943-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9955168. Licensed CC0.

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