# Dynamics and mechanisms of filovirus envelop glycoproteins

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2024 · $782,818

## Abstract

SUMMARY
The increasing frequency and severity of Ebola outbreaks demands an expanded repertoire of treatments and
preventative measures. Answering this unmet need will require a deeper understanding of the molecular
mechanisms underlying filovirus replication. In particular, the dynamic events that occur during filovirus envelope
glycoprotein (GP)-mediated membrane fusion during entry into cells have evaded elucidation for decades.
Previous studies have identified proteolytic cleavage of GP, receptor binding, and the chemical environment of
the late endosome as being critical. But the molecular mechanisms by which these events and variables promote
GP-mediated membrane fusion are not known. As a result, a complete and specific model of filovirus fusion,
which integrates host factors, environmental conditions, and GP conformational changes currently does not exist.
Therefore, filovirus entry continues to be an unutilized target for inhibitors. Our long-term goal is to develop a
complete mechanistic model of GP-mediated membrane fusion. Our recent publications, in which we
demonstrate the power of single-molecule fluorescence methods in elucidating the conformational dynamics of
EBOV GP on the surface of virions, demonstrate our initial efforts toward this end. Here we aim to build on this
success by proposing a multidisciplinary study involving virological, cellular, structural, and biophysical
methodologies to elucidate the dynamics and mechanisms of GPs from multiple filoviruses. We will characterize
the mechanisms by which conformational changes, host factors, and environmental variables facilitate filovirus
membrane fusion and entry into cells. Completion of the proposed research will provide mechanistic insights into
filovirus entry and the viral and host targets that could be exploited with novel therapies and immunogens.

## Key facts

- **NIH application ID:** 10886761
- **Project number:** 5R01AI174645-03
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** James B Munro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $782,818
- **Award type:** 5
- **Project period:** 2022-09-19 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10886761

## Citation

> US National Institutes of Health, RePORTER application 10886761, Dynamics and mechanisms of filovirus envelop glycoproteins (5R01AI174645-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10886761. Licensed CC0.

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