# Identification of Host Directed Drug Targets for SARS-CoV-2 Using Transposon Mutagenesis

> **NIH NIH R21** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $442,750

## Abstract

SUMMARY
The ongoing SARS-CoV-2 pandemic has brought into stark relief the need for novel therapeutics that can work
against a broad spectrum of coronaviruses. Identifying essential host genes involved in both virus replication
and antiviral defense could reveal key host-directed viral therapies that have the potential to work against
SARS-CoV-2 and future coronavirus outbreaks. The overarching goal of our laboratory is to identify
mechanisms of host defense against viral infections. This application aims to identify both host-encoded
mechanisms of resistance to infection by SARS-CoV-2 as well as cellular factors critical for virus replication.
Based on emerging data and our preliminary studies, our central hypothesis is that the up-regulation of host
‘restriction factors’ that prevent viral entry, constrain virus replication in host cells, or increase the ability of cells
to withstand viral-induced cytopathy represent an important strategy in host defense. Our rationale for the
proposed work is that identification of such factors will provide new targets for therapeutic intervention, and that
these may be less susceptible to resistance than viral-encoded targets. We will use a novel forward-genetic
approach to screen for host genes that confer resistance to SARS-CoV-2 infection in BSL3 using the native
virus. This will allow us to identify key targets at all stages of virus infection. We will then validate new host
targets and use these insights to rationally develop antiviral therapeutic strategies. Our screening approach is
innovative because it allows identification of both host genes that confer resistance as well as host genes
required for infection, which are normally detected in conventional RNAi-based screens. This work has the
potential to identify new targets, including non-coding RNA elements, which would be missed using existing
approaches.

## Key facts

- **NIH application ID:** 10238213
- **Project number:** 1R21AI161275-01
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Anna Bruchez
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $442,750
- **Award type:** 1
- **Project period:** 2021-07-06 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10238213

## Citation

> US National Institutes of Health, RePORTER application 10238213, Identification of Host Directed Drug Targets for SARS-CoV-2 Using Transposon Mutagenesis (1R21AI161275-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10238213. Licensed CC0.

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