# SERPINs as a novel family of innate antiviral molecules - Resubmission - 1

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $211,875

## Abstract

PROJECT SUMMARY
The primary goal of this R21 proposal is to characterize and systematically identify novel host serine protease
inhibitors (SERPINs) that restrict replication of three clinically important respiratory viruses. Although respiratory
viruses pose a major health burden, there is a lack of effective treatment options. Understanding the mechanisms
by which host factors inhibit these viral infections may lead to novel antiviral strategies. The project is founded
on our recent discovery that one SERPIN family member, SERPINE1, inhibits influenza A virus by targeting
airway proteases that the virus requires for glycoprotein maturation. This study opened the door for a novel
concept in innate immunity: that SERPINs may constitute a previously unappreciated class of antiviral factors.
The main technical innovation of this proposal is the use of stratified polarized airway epithelium cultures (HAEC)
inducibly expressing individual SERPINs from a recently assembled library. These HAEC display the entire
arsenal of endogenous intra- and extracellular airway proteases, a number of which play important roles in
respiratory virus life cycles. This proteolytic environment allows for a more unbiased discovery of SERPINs that
inhibit endogenous airway proteases and thereby may restrict replication of specific respiratory viruses. We are
combining this 3D tissue culture technology with confocal high-content imaging, directly on the polarized cultures.
Completion of our aims may provide a novel facet of the innate immune response: modulating proteolytic tissue
environments to inhibit viruses.

## Key facts

- **NIH application ID:** 9848488
- **Project number:** 5R21AI139374-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Meike Dittmann
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $211,875
- **Award type:** 5
- **Project period:** 2019-01-09 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9848488

## Citation

> US National Institutes of Health, RePORTER application 9848488, SERPINs as a novel family of innate antiviral molecules - Resubmission - 1 (5R21AI139374-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9848488. Licensed CC0.

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