# Optimizing Zika NS5 Methyltransferase Inhibitors

> **NIH NIH R21** · UNIVERSITY OF MINNESOTA · 2021 · $231,875

## Abstract

ABSTRACT
Zika Virus (ZIKV) has emerged as a global public health threat because of its recent outbreaks and its link to
microcephaly in newborns and Guillain-Barré syndrome in adults. To date, there is no vaccine or treatment
available, highlighting an urgent need to develop effective therapeutics. Inhibition of ZIKV NS5 methyltransferase
(MTase) is a promising anti-ZIKV strategy. However, current ZIKV MTase inhibitors generally suffer from low
activity, lack of selectivity, or unfavorable drug-like properties, hindering testing of MTase inhibitors in the animal
models of ZIKV infection. We have designed and synthesized a structurally novel inhibitor of ZIKV NS5 MTase,
which possessed anti-ZIKV activity without significant toxicity. In this application, we will perform lead
optimization to improve the potency, selectivity and drug-like properties of our ZIKV MTase inhibitors, aiming to
identify MTase inhibitors that can be used in the ZIKV animal disease models. To accomplish the goal, we
propose the following specific aims: Specific Aim 1. Design and synthesize ZIKV NS5 MTase inhibitors and
evaluate them in biochemical and antiviral assays; Specific Aim 2. Assess selected ZIKV NS5 MTase inhibitors
for their physiochemical and in vitro absorption, distribution, metabolism, and excretion (ADME) properties; and
Specific Aim 3. Determine in vivo PK parameters of advanced ZIKV NS5 MTase inhibitors. We expect that the
proposed research will significantly contribute to efforts in developing ZIKV MTase inhibitors as anti-ZIKV
therapeutics.

## Key facts

- **NIH application ID:** 10092108
- **Project number:** 5R21AI151427-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Liqiang Chen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $231,875
- **Award type:** 5
- **Project period:** 2020-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10092108

## Citation

> US National Institutes of Health, RePORTER application 10092108, Optimizing Zika NS5 Methyltransferase Inhibitors (5R21AI151427-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10092108. Licensed CC0.

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