# Adaptive MERS coronavirus-cell entry pathways and their relevance to virulence and antiviral strategies

> **NIH NIH P01** · UNIVERSITY OF IOWA · 2021 · $266,291

## Abstract

PROJECT SUMMARY
The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a zoonotic virus
that can cause fatal disease in patients with underlying comorbidities. Further
recognition of this respiratory syndrome and prevention strategies will require a small
animal infection model as well as an additional understanding of the virus. This PPG
describes a mouse model of MERS-CoV disease. In this model, the viruses causing
disease are adapted variants, specialized for mouse lung infection. By contrast, non-
adapted MERS-CoVs cause infection in the mouse but do not cause disease. The
central hypothesis of this subproject (PPG2) is that mouse-adapted variants can
efficiently enter host cells through pathways that are not available to the non-adapted
viruses. To address this hypothesis, recombinant MERS-CoVs will be constructed and
evaluated to determine whether mouse-adaptive mutations in the cell entry-mediating
viral spike proteins correlate with efficient mouse lung infection. Surrogate MERS-CoV
pseudo-viruses will be constructed and evaluated to address the focused hypothesis that
mouse adapted variants mediate an “early” plasma-membrane cell entry that is
unavailable to non-adapted viruses. The project will dissect mechanisms by which spike
proteins mediate early cell entry through plasma membranes versus late cell entry
through endosomes. The basis for selection of early versus late cell entry will be
determined by identifying host cell factors promoting or restricting either pathway. This
project will also identify appropriate antiviral strategies that operate by preventing early
and late virus-cell entry. The rationale for all of these aims is that additional
understanding of MERS-CoV cell entry pathways will identify correlates of robust
infection and disease, and will also provide insights on the best ways to prevent infection
and disease with innovative virus entry inhibitors.

## Key facts

- **NIH application ID:** 10229391
- **Project number:** 5P01AI060699-15
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Thomas Miller Gallagher
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $266,291
- **Award type:** 5
- **Project period:** 2004-07-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229391

## Citation

> US National Institutes of Health, RePORTER application 10229391, Adaptive MERS coronavirus-cell entry pathways and their relevance to virulence and antiviral strategies (5P01AI060699-15). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10229391. Licensed CC0.

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