# SARS-CoV adaptations through a Systems Biology Lens (SYBIL)

> **NIH NIH U19** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $2,534,738

## Abstract

Previous to the COVID-19 pandemic, we assembled, under the same U19 mechanism, a multidisciplinary
team to obtain multiple OMICS-based systems level measurements and integrate them using modeling
approaches and machine learning algorithms to identify and validate host-virus networks that modulate
influenza A virus disease severity, biomarkers in blood that reflect the activation states of these networks and
novel host targets for therapeutic interventions. As a result, we have identified important host factors and
pathways involved in antiviral response and virus replication and disease, leading to potential treatments. The
sudden onset of the COVID-19 pandemic in 2020 prompted us to redirect our systems biology efforts to study
SARS-CoV-2 infections. We now propose to continue these studies under this U19 renewal application entitled
SARS-CoV adaptations through a Systems Biology Lens (SYBIL). Our underlying main hypothesis is that
host networks involved in SARS-CoV replication and early host responses regulate disease outcomes and
represent targets for therapeutic intervention. As these viruses have a zoonotic origin in bats, we will also
explore virus-host networks involved in human adaptation and responsible for changing the tropism from the
original bat host to humans. In order to identify clinically relevant networks involved in SARS-CoV replication,
pathogenesis and host tropism we propose to integrate into predictive and comprehensive models global
responses during infection in three systems 1) human blood and respiratory samples from human cohorts with
documented SARS-CoV infection and diverse clinical outcomes (Project 1); 2) blood and tissues from
experimentally infected animals under a variety of conditions and perturbations resulting in diverse disease
outcomes (Project 1) and 3) human and bat cells subjected to viral protein expression, genetic screens and
infection with diverse SARS-CoVs, including primary cells derived from iPSC precursors (Project 2). Samples
will be processed and send to the Technology Core for global transcriptomics, epigenetics, proteomics and
functional genomics analysis. OMICS data sets will be integrated and compared by the Modeling Core to
generate specific hypothesis and network models of disease, uncover blood biomarkers and identify host and
virus key drivers of viral replication, host response, disease outcome and host tropism. Predicted network
regulators will be used as a source for subsequent iterative rounds of perturbations to refine existing and to
identify new network models. Data and models will be managed and disseminated by the Data Management
and Bioinformatics Core. We expect that these studies will uncover novel virus-host pathogenic networks,
blood biomarkers associated with them, determinants of human adaptation and specific therapeutic targets. In
summary, our modeling approaches will find associations between diverse experimental systems that will help
us define determinants associated...

## Key facts

- **NIH application ID:** 10758529
- **Project number:** 5U19AI135972-07
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Adolfo Garcia-Sastre
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,534,738
- **Award type:** 5
- **Project period:** 2018-01-20 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10758529

## Citation

> US National Institutes of Health, RePORTER application 10758529, SARS-CoV adaptations through a Systems Biology Lens (SYBIL) (5U19AI135972-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10758529. Licensed CC0.

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