# Elucidation of host factors required for Powassan virus replication as potential therapeutic targets

> **NIH NIH R03** · ROCKEFELLER UNIVERSITY · 2020 · $84,750

## Abstract

Project Summary
Powassan virus (POWV) is a tick-borne flavivirus that can be transmitted to humans and causes
symptoms including fever, vomiting, headache, and generalized weakness. The disease can progress
to meningoencephalitis, resulting in altered mental status, seizures, aphasia, and paresis amongst
other signs. Survivors of symptomatic disease are often left with residual sequelae and there is no
specific treatment available. This study will identify host factors that POWV requires for its replication,
focusing on human factors for which inhibitory drugs can potentially be developed. In the first aim,
CRISPR/Cas9 will be used to knock out genes for factors previously identified as required for
replication of two other flaviviruses and for which drugs could be developed. The knockout cells will
be challenged with POWV and replication assessed. For those genes with identified drug interactions,
wildtype cells will be treated with various doses of drugs targeting the factors and replication
assessed to determine if the drugs inhibit POWV replication. In the second aim a CRISPR/Cas9
knockout library based on the druggable human genome will be generated and used to screen for
potentially druggable host factors required by POWV for replication and cell killing. These factors
would be targets for drug development in future studies.

## Key facts

- **NIH application ID:** 9851341
- **Project number:** 5R03AI141855-02
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** MARGARET R MACDONALD
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $84,750
- **Award type:** 5
- **Project period:** 2019-01-17 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851341

## Citation

> US National Institutes of Health, RePORTER application 9851341, Elucidation of host factors required for Powassan virus replication as potential therapeutic targets (5R03AI141855-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9851341. Licensed CC0.

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