# Organ-on-Chip Approach for Assessing Tissue-specific SARS-CoV-2 Infection and Response to Antiviral Therapy

> **NIH NIH R44** · NORTIS, INC. · 2020 · $255,716

## Abstract

The current COVID-19 pandemic is a worldwide, rapidly developing, health crisis caused by the Severe Acute
Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). As of May 18, 2020, over 4.7 million infections are
confirmed globally and over 315,000 people have died from COVID-19 related complications. Efforts to develop
and test COVID-19 vaccines are in high gear. In the meantime, there is a dire need for fast and robust in-vitro
tests that can be used to study the mechanisms of host-virus interactions and help assess whether existing
antivirals could be used against for SARS-CoV-2. Current static 2D cell culture systems and animal-based
models are of limited use for these purposes. To address this gap, the proposed project aims to develop organ-
on-chip (OOC)-based assays for quantifying SARS-CoV-2 inoculation and replication in three human tissues
that have been shown to be severely affected by SARS-CoV-2. In order to enable an immediate start, a fast
timeline, and milestones with translational impact, the approach of this supplement will mainly repurpose already
existing, validated, and commercialized OOC models that were developed under the parent grant. AIM1 is to
develop SARS-CoV-2 assays for kidney proximal tubule and vascular endothelium, models that were initially
developed for assessing drug toxicity and drug transport. In addition, an OOC model of the lung alveolus will be
developed. SARS-CoV-2 Wuhan Reference Strain, the SARS-CoV-2 Spike Mutation D614G Strain, as well as
a Spike-pseudotyped lentivirus will be tested and compared for differences in inoculation rate and replication
rate (AIM2). The assay protocols will include introducing the viruses via the perfusate to the lumen of the tissue
structures in order to bring the virus in contact with the ACE2 and CD 147 receptors that reside on the apical
side of the cell and are responsible for virus binding and subsequent endocytosis. To quantify viral inoculation,
the tissues will be removed after a short but adequate incubation period. The viruses will be extracted from the
tissues, serially diluted and quantified using plaque assays. In order to assess viral replication, tissues will be
harvested from the chips after a pre-determined, longer, incubation period that gives the cells enough time for
viral replication. Viral load will be quantified with plaque assays. AIM3 is to use the OOC-based assays for testing
a number of candidate antivirals and compare their effect against baseline SARS-COVID-19 virus load. The list
of antivirals to be tested includes antibodies against ACE2 and CD147 receptors; RNA polymerase inhibitor
Remdesivir; PAMP RNA, a RIG-agonist and interferon inducer; and the antimalarial chloroquine. The data
obtained from the OOC assays will be correlated with pre-existing in-vitro data, animal data, and clinical findings.
The technology can be quickly made available to the research community. Models of other tissue structures
affected by SARS-COVID-19, such as myocardium,...

## Key facts

- **NIH application ID:** 10171540
- **Project number:** 3R44TR003065-02S1
- **Recipient organization:** NORTIS, INC.
- **Principal Investigator:** Thomas Neumann
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $255,716
- **Award type:** 3
- **Project period:** 2019-09-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10171540

## Citation

> US National Institutes of Health, RePORTER application 10171540, Organ-on-Chip Approach for Assessing Tissue-specific SARS-CoV-2 Infection and Response to Antiviral Therapy (3R44TR003065-02S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10171540. Licensed CC0.

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