# Innate responses following infection with enteric microbes

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $354,469

## Abstract

ABSTRACT
As the rapidly unfolding COVID-19 pandemic claims its victims around the world, it has also inspired the scientific
community to come up with solutions to meet an urgent and unmet need —i.e., ameliorate the severity of Covid-
19 and reduce mortality. Two obstacles make that task difficult—First, the pathophysiology of Covid-19 remains
a mystery; the emerging reports generally agree that the disease has a very slow onset and that those who
succumb typically mount a ‘cytokine storm’, i.e., an overzealous immune response. However, despite being
implicated as a culprit behind the observed mortality and morbidity in COVID-19, we know virtually nothing about
what constitutes (nature, extent) or contributes to (cell or origin) such an overzealous response. A significant
number of patients have GI symptoms. The treatment goals in COVID-19 have been formulated largely as a ‘trial
and error’-approach; this is reflected in the mixed results of the trials that have concluded. Second, the process
of drug discovery is comprised of time-consuming steps; to avoid delays, we need to define the nature of the
fatal cellular response before deciding how to model it in animals or matching therapeutics to curb it.
 Our preliminary work has helped us define the aberrant host cellular response in COVID-19. We used
machine learning tools that can look beyond interindividual variability to extract underlying gene expression
patterns within complex data across multiple cohorts of viral pandemics, including COVID-19. The resultant
pattern, i.e., signature, was subsequently exploited as a predictive model to navigate COVID-19 for GI
symptoms. Surprisingly, the 166-gene signature was conserved in all viral pandemics, including COVID-19,
inspiring the nomenclature-- (ViP)-signature. The ViP signature identified and predicted the disease severity of
SARS-CoV2-infected patients. We hypothesized that the ViP signature provides a quantitative and qualitative
framework for titrating the cellular response in viral pandemics and could serve as a powerful unbiased tool in
our armamentarium to vet candidate drugs rapidly. In this proposal, our predicted model, experimental datasets
and the information from published literature will be used to screen drugs/nutritional components/probiotics in
the GI organoid derived monolayers in a semi-HTP format. We will experimentally validate the effect of the
therapeutics predicted in ViP gene signature of the host. The following two aims will provide a translational impact
on the COVID-19 emergency.
Aim 1: Identify the gastro-intestinal pathogenic pathways during COVID-19.
Aim 2: Determine the impact of drugs, nutrients and supplements in gut-in-a-dish model of COVID-19.
Impact: This proposal will identify the gastro-intestinal pathways (in healthy and patients with chronic diseases)
involved in the GI symptoms of COVID 19 and provide new treatment options in COVID-19.

## Key facts

- **NIH application ID:** 10177672
- **Project number:** 3R01DK107585-05S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Soumita Das
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $354,469
- **Award type:** 3
- **Project period:** 2016-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177672

## Citation

> US National Institutes of Health, RePORTER application 10177672, Innate responses following infection with enteric microbes (3R01DK107585-05S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10177672. Licensed CC0.

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