# Structural Studies of Coronavirus Fusion Proteins

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $294,397

## Abstract

Enveloped viruses use specialized proteins present at the virus surface to translocate their genetic
material across the host cell membrane during infection. For coronaviruses, homotrimers of the spike
glycoprotein promote host cell attachment and fusion of the viral and host membranes. Although
coronaviruses have a significant pandemic potential, the lack of high-resolution data for any
coronavirus spike trimer limits our mechanistic understanding of infection by this family of viruses.
The objective of the proposed work is to obtain high-resolution snapshots corresponding to the
various stages of the fusion reaction mediated by coronavirus spikes and to study the structural
determinants associated with antibody inhibition of viral infection. In Aim I, we propose to elucidate
the architecture of the Mouse Hepatitis Virus (MHV) pre-fusion spike using cryoEM. Aim II will be
dedicated to studying the conformational changes associated with the fusion reaction with an
emphasis on the first intermediate (extended intermediate) and the post-fusion spike. In Aim III, we
will characterize the 3D organization of human coronavirus spikes to understand how these viruses
overcome the species barrier and to identify structurally conserved regions that could be potential
targets for therapeutic initiatives. The final aim will rely on structure-guided protein design to engineer
antibodies targeting human coronavirus spikes with the goal of identifying immunogens for raising
broadly-neutralizing antibodies.

## Key facts

- **NIH application ID:** 9997973
- **Project number:** 5R01GM120553-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** David Veesler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $294,397
- **Award type:** 5
- **Project period:** 2016-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997973

## Citation

> US National Institutes of Health, RePORTER application 9997973, Structural Studies of Coronavirus Fusion Proteins (5R01GM120553-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9997973. Licensed CC0.

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