# Identification of Small Molecular Inhibitors of Rift Valley Fever Virus Replication

> **NIH NIH R21** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $200,337

## Abstract

Project Summary
 Rift Valley fever caused by Rift Valley fever virus (RVFV) is an acute, mosquito-borne, fever-causing
zoonotic disease that affects both humans and animals. Large Rift Valley fever outbreaks have occurred
throughout Africa and more recently in the Arabian Peninsula. Because RVFV is no longer restricted to African
countries, it has raised concerns that the disease could spread worldwide. The RVFV is a select agent that
requires high biocontainment facilities. This limitation has hampered the development of RVFV antivirals and
vaccines. Despite the significant impact of the disease to the economy and public health, there are no fully
licensed vaccine and antivirals available in the US for human and animal use. It is urgent to identify and develop
effective inhibitors against RVFV to treat exposed and infected humans and animals.
 Dr. Ma’s group has developed a cell-based screening assay based on the RVFV MP12 vaccine strain that
expresses Renilla Luciferase using Renilla as readout to identify RVFV inhibitors, and established a STAT1-KO
mouse model susceptible to infection with MP12 vaccine strain that can be used in a BSL-2 facility. Furthermore,
they have screened 727 compounds from the NIH collections of which two candidates including 6-azauridine
and mitoxantrone inhibited replication of MP12. They hypothesize that effective inhibitors against RVFV can be
identified by screening large compound collections and by further optimization of their structures and activities,
and the mechanisms of inhibitory effects of identified candidates can be determined. Thus, they plan to use the
developed high-throughput assay to identify inhibitors against RVFV, evaluate their efficacy in vitro and in mice,
and understand the underlying mechanisms of inhibitory effects of identified candidates through two specific
aims in this R21 proposal. In specific aim 1, the libraries assembled by the University of Kansas High Throughput
Screening Laboratory that contain approximately 26,000 chemical compounds will be screened. The 26,000
compounds are predicted to cross the blood-brain barrier. Hits from the library will help overcome the challenge
for RVFV antivirals to reach the brain through the blood-brain barrier to protect encephalitis. Primary hits will be
confirmed by in vitro and in vivo assays. In specific aim 2, 6-azauridine and mitoxantrone as well as others
identified in Aim 1 will be evaluated in vitro and in the BALB/c mice using virulent RVFV. To understand the
underlying mechanisms of their inhibitory effects, whether the compounds block virus entry, inhibit virus
replication and polymerase activity will be investigated using different designed assays. The results of this study
could identify novel effective inhibitors against RVFV and understand the underlying mechanisms of their
inhibitory effects, and offer novel insights toward the design of novel antiviral drugs against this zoonotic disease
that will benefit both human and animal he...

## Key facts

- **NIH application ID:** 10192049
- **Project number:** 7R21AI128377-02
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Wenjun Ma
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $200,337
- **Award type:** 7
- **Project period:** 2020-02-08 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10192049

## Citation

> US National Institutes of Health, RePORTER application 10192049, Identification of Small Molecular Inhibitors of Rift Valley Fever Virus Replication (7R21AI128377-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10192049. Licensed CC0.

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