# Kidney Microphysiological Analysis Platforms (MAP) to Explore SARS-CoV-2 Receptors and Inhibitors. A supplement to Parent Grant: Kidney Microphysiological Analysis Platforms (MAP) to Optimize Function

> **NIH NIH UH3** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $251,531

## Abstract

Abstract
Coronavirus disease 2019 (COVID-19) has reached pandemic proportions. Pulmonary and
kidney disease are highly prevalent serious consequences of infection with SARS-CoV-2. Kidney
Injury Molecule-1 (KIM-1) was identified by Drs Bonventre and Ichimura as the most upregulated
protein in the injured kidney proximal tubule. KIM-1, also called TIM-1, is a receptor for hepatitis
A, Ebola, Dengue and possibly SARS-CoV1 viruses. We hypothesize that KIM-1 is a receptor
for SARS-CoV-2 both in renal tubule epithelial cells and in airway epithelial cells and that
JB1, our newly discovered small molecule inhibitor of KIM-1, and/or nanodisc-
incorporated KIM-1 ectodomain can be prophylactic and therapeutic agents for COVID-19.
We also hypothesize that we can use the high-affinity binding of KIM-1 and ACE2 to the
virus to create novel diagnostic devices for the virus. In Specific Aim 1 we will characterize
the role of KIM-1 in promoting SARS-CoV-2 entry into kidney and lung epithelia using kidney
microphysiological analysis platforms (MAPs) on chip and develop an ultrasensitive chip for the
high-throughput evaluation of potential SARS-CoV-2 binding inhibitors. KIM-1 and ACE2
mediated endocytosis of SARS-CoV-2 biomimetic viruses (virosomes) will be compared in kidney
and lung epithelial cells. We will evaluate the effects of KIM-1-mediated spike proteins or
biomimetic virus cellular adhesion and uptake on production of paracrine factors which activate
endothelial cells using a kidney-lung MAP. In order to understand binding and/or uptake kinetics
of SARS-CoV-2 and characterize potential inhibitors we will develop an ultrasensitive
nanoplasmonic triplets-based rapid lateral flow diagnostic chip for a rapid and sensitive inhibition
assay using the kidney-lung MAP. This approach can also be used for point of care diagnostic
testing for the virus. In Specific Aim 2 we will evaluate the efficacy of JB1, soluble KIM-1
ectodomain and nanodisc-incorporated KIM-1 or ACE2 to inhibit binding and internalization of
SARS-CoV-2 biomimetic viruses by kidney and lung cells using an integrated lung-kidney MAP
on chip. Potential inhibitors will be tested to evaluate whether they compete with S-protein and/or
biomimetic virus binding and reduce IL-6 production. Binding affinity and kinetics between KIM-1
variants or ACE2 either as free ectodomains or incorporated into nanodiscs and the Spike protein
will be measured using MicroScale Thermophoresis (MST) and Biolayer Interferometry.

## Key facts

- **NIH application ID:** 10179916
- **Project number:** 3UH3TR002155-04S1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** JOSEPH VINCENT BONVENTRE
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $251,531
- **Award type:** 3
- **Project period:** 2017-07-25 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10179916

## Citation

> US National Institutes of Health, RePORTER application 10179916, Kidney Microphysiological Analysis Platforms (MAP) to Explore SARS-CoV-2 Receptors and Inhibitors. A supplement to Parent Grant: Kidney Microphysiological Analysis Platforms (MAP) to Optimize Function (3UH3TR002155-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10179916. Licensed CC0.

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