# Vascular, Cardiac, and Lung Alveolar Human Microphysiological Systems for SARS-CoV-2 Drug Screening

> **NIH NIH UH3** · DUKE UNIVERSITY · 2020 · $280,600

## Abstract

Abstract
The appearance of SARS-CoV-2 in early 2020 has spurred efforts to limit the disease spread and develop
effective treatments. The most promising long-term approach is a vaccine. While some vaccines are entering
accelerated clinical trials, it may take 12 or more months before an effective vaccine is available. Even if
successful, it may not be possible to treat everyone with a vaccine or the effectiveness of the vaccine may be
limited. Given the severity of the disease among a number of those patients, alternative approaches to limit
infection should be developed. The goal of this proposal is to use human cardiac, vascular, and lung alveolar
microphysiological systems (MPS) to identify possible compounds that block SARS-CoV-2 entry into cells and
tissues. While cell binding assays can be used to screen drug candidates, human MPS offer the advantage of
testing promising drug candidates under conditions encountered in the body. We propose a tiered approach in
which primary cells and cells overexpressing angiotensin converting enzyme (ACE2) are used to identify
promising candidates that block SARS-CoV-2 virus entry into cells, and vascular, cardiac, and lung alveolar
MPS are used to provide a robust evaluation of drugs that block SARS-CoV-2 binding. The first tier with
individual cell types enables a rapid screen and the screen with the microphysiological systems enables testing
of the most promising candidates with the tissues most likely to be infected. We will develop the screening
assays using a pseudovirus with the SARS-CoV-2 spike protein. In Aim 1, we will develop an assay for
pseudovirus binding to ACE2 expressing cells by verifying binding and fusion to cells that express ACE2. We
will whether the binding specifically involves the spike protein and determine the levels of binding sites on the
cell types used in subsequent aims. In Aim 2, we will screen individual cells types for molecules that block
entry into the cell of pseudovirus expressing the spike proteins. Potential drug candidates include those that
potentially block spike protein binding (e.g. spike proteins, Captopril, Lisinopril, human recombinant soluble
ACE2, and antibodies to the spike protein or ACE2) and those inhibiting Transmembrane Serine Protease 2
(TMPRSS2), activity (e.g. camostat mesylate, nafamostat mesylate). In Aim 3, we will test most promising
compounds in vascular, cardiac and lung microphysiological systems and compare against results from 2D
studies. We will also examine the relationship between drug blocking and factors that affect ACE2 expression.

## Key facts

- **NIH application ID:** 10166020
- **Project number:** 3UH3TR002142-04S1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** George A Truskey
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $280,600
- **Award type:** 3
- **Project period:** 2017-08-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166020

## Citation

> US National Institutes of Health, RePORTER application 10166020, Vascular, Cardiac, and Lung Alveolar Human Microphysiological Systems for SARS-CoV-2 Drug Screening (3UH3TR002142-04S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10166020. Licensed CC0.

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