# Design of fusion inhibitors to block measles host-to-host infection

> **NIH NIH R56** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $561,162

## Abstract

Measles (MeV) causes disease worldwide despite efforts towards eradication by
vaccine, largely because it is spread so readily between people. Acute MeV infection
causes immune amnesia, resulting in increased susceptibility to other infectious
diseases. In addition, rare but severe neurological complications can develop several
years after measles due to persistent MeV infection of the central nervous system.
People with impaired cellular immunity are at increased risk of developing severe
measles, but often cannot be vaccinated since the vaccine virus itself can lead to fatal
illness. There is no specific therapy for acute or persistent MeV manifestations. A
successful vaccination campaign could have eradicated MeV more than 20 years ago.
As today, mainly due to social issue (e.g., antivaxxer movement), eradication is not in
sight. The recent resurgence of measles in the U.S. highlights the need of effective
measure to prevent host-to-host transmission at the moment of the outbreak surge.
We have applied the results of fundamental research to develop a new antiviral strategy
for MeV, based on inhibiting membrane fusion during MeV entry. This application will
test whether our antiviral approach prevents inter-host transmission and therefore fill this
medical demand. Our strategy is based MeV fusion inhibitors (i.e., lipid conjugated
peptides) that self-assemble in stable nanoparticles until they reach the target cells
were, they integrated into the cell membrane.
 We have recently shown that this strategy works effectively for SARS-CoV-2.
We propose to chemical engineer these inhibitors to optimize 1) the antiviral potency, 2)
the conditions under which the peptides self-assemble, 3) the insertion on the target cell
membrane, and 5) in vivo biodistribution.
Our work will be tested in vitro, ex vivo, and in vivo using a natural model of morbillivirus
infection (Canine Distemper Virus -CDV- in Ferrets).
1. To use protein engineering to optimize the self-assembling properties and
antiviral potency of HRC-peptide fusion inhibitors.
2. To evaluate the protection afforded by HRC peptide fusion inhibitors against
CDV infection in vivo and provide proof of concept for pre-clinical development.

## Key facts

- **NIH application ID:** 10457081
- **Project number:** 1R56AI159085-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Matteo Porotto
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $561,162
- **Award type:** 1
- **Project period:** 2021-08-09 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10457081

## Citation

> US National Institutes of Health, RePORTER application 10457081, Design of fusion inhibitors to block measles host-to-host infection (1R56AI159085-01A1). Retrieved via AI Analytics 2026-07-26 from https://api.ai-analytics.org/grant/nih/10457081. Licensed CC0.

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