# Project 2 - Ex Vivo Analysis of Coronavirus Tropism, Adaptation, Replication, and Host Response

> **NIH NIH U19** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $702,405

## Abstract

PROJECT 2: Ex Vivo Analysis of Coronavirus Tropism, Adaptation, Replication, and Host Response
 In this proposal, we hypothesize that multiple and discrete virus-host interactions and host responses to
infection dictate the pathogenic outcome and host tropism of SARS-CoV-2. We further hypothesize that these
critical circuits can be dissected through network-based modeling of system-level measurements offering the
potential for the development of novel antiviral therapies. In Project 2, we propose to utilize leading edge OMICs-
based measurements to define virus-host interactions and networks that control viral replication, viral
tropism/adaptation and host responses across bat coronaviruses, SARS-CoV-1, and SARS-CoV-2 variants. In
Aim 1, we will conduct proteomics (AP-MS, protein abundance and post-translational modifications),
transcriptomics (RNA-seq and scRNA-seq), epigenomics (ATAC-seq, Hi-C and ChiP-seq) and genetic and
chemical compound screens using ex vivo primary epithelial cells and iPSC-derived pneumocytes derived both
from human and bats and a lung epithelial cell line (A549). In Aim 2, these data will be integrated and modeled
with in vivo and clinical data collected in Project 1 using network-based predictive modeling approaches to
identify host proteins, networks, and pathways that correlate with disease severity and host adaptation (‘driver
genes’). Reiterative modeling of data generated in Aim 1 and Project 1 will be employed to refine these
predictions. In Aim 3, CRISPR-editing approaches will be used in concert with targeted OMICs measurements
(CRISPR-OMICs), including transcriptional, epigenetic, proteomic analyses, to validate the impact of these
‘driver genes’ on disease outcome and host tropism. Additional molecular, cellular, biochemical, and in vivo
studies will be conducted to further characterize nodes that determine disease outcome as potential therapeutic
targets. Overall, these studies will enable us to correlate in vivo and clinical biomarkers predictive of COVID-19
severity (Project 1) to specific genes and networks that impact viral infection, cellular host responses, and
interspecies transmission.

## Key facts

- **NIH application ID:** 10758552
- **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:** $702,405
- **Award type:** 5
- **Project period:** 2018-01-20 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10758552

## Citation

> US National Institutes of Health, RePORTER application 10758552, Project 2 - Ex Vivo Analysis of Coronavirus Tropism, Adaptation, Replication, and Host Response (5U19AI135972-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10758552. Licensed CC0.

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