# Discovery of novel flavivirus inhibitors

> **NIH NIH U19** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2022 · $2,677,020

## Abstract

PROJECT 4 – ABSTRACT
The goal of this project is to discover novel flavivirus inhibitors. Novartis has 15-year historical data in dengue
polymerase, protease, and nucleoside/nucleotide collection. The data sets are ideal for machine-learning
pQSAR to rationally explore/design new chemical matters against these proven antiviral targets. We will pursue
three aims. (i) Discover a NS5 nucleoside polymerase inhibitor. Nucleoside/nucleotide inhibitors form the major
class of clinically approved antiviral drugs. It has the advantages of high resistance barrier and broad-spectrum
antiviral activity. The latter advantage can be capitalized to synergize with other projects by testing the
nucleoside/nucleotide compounds against viruses from different families. (ii) Discover a NS5 non-nucleoside
polymerase inhibitor. We have generated a large dataset of dengue polymerase inhibitors from previous HTS
campaigns. These HTS campaigns were performed using different biochemical and biophysical assays. A
proprietary machine-learning platform, together with established biochemical and structural biological tools, will
be used to guide a rational drug discovery. (iii) Discover a NS3 protease inhibitor. We will develop a non-
peptidomimetic inhibitor of flavivirus protease, leveraging on our previous expertise on dengue protease (e.g.,
cocrystal structure of dengue NS2B cofactor and protease in complex with an inhibitor) and Novartis’ other
protease projects.

## Key facts

- **NIH application ID:** 10514155
- **Project number:** 1U19AI171413-01
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Fumiaki Yokokawa
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,677,020
- **Award type:** 1
- **Project period:** 2022-05-16 → 2025-03-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10514155

## Citation

> US National Institutes of Health, RePORTER application 10514155, Discovery of novel flavivirus inhibitors (1U19AI171413-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10514155. Licensed CC0.

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