# Artemisinin activation in artemisinin resistant malarial parasites

> **NIH NIH R21** · GEORGETOWN UNIVERSITY · 2021 · $191,150

## Abstract

Currently artemisinin (ART) combination therapies (ACTs) are the only universally effective
treatments vs all malaria worldwide. Troublingly however, a harbinger of ART drug resistance (ArtR) has
emerged in South East Asia, referred to as the "delayed clearance phenotype" (DCP). Elucidation of the
molecular mechanism of DCP/ArtR is one of the most pressing issues in infectious disease research today.
Multiple genetic determinants have been described for DCP, with the most common being mutations in the
PfK13 gene, but currently no single unifying molecular mechanism for DCP is known. Our group has been
the first to apply targeted metabolomics to the analysis of ART drug pharmacology and ArtR. In essence
our malarial parasite culture, fractionation, and extraction methods, combined with liquid chromatography -
mass spectrometry (LCMS) techniques, have allowed us to quantify, for the first time, ART drug - FPIX
heme covalent adducts formed within live malarial parasites. Our hypothesis is that ART drug - FPIX
heme adduct formation correlates with ArtR, and that adduct abundance predicts the severity of ArtR ("fold"
ArtR). We will use these newly perfected methods to test the attractive hypothesis that adduct abundance is
correlated with the degree of severity of evolving ArtR. Our work will be comprehensive and span analysis
of adducts formed vs multiple natural and synthetic ART drugs and ACT combinations, as well as multiple
types of ArtR parasites that harbor all common PfK13 mutations or that do not appear to harbor PfK13
mutations at all.

## Key facts

- **NIH application ID:** 10115597
- **Project number:** 5R21AI146506-02
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** PAUL D. ROEPE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $191,150
- **Award type:** 5
- **Project period:** 2020-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115597

## Citation

> US National Institutes of Health, RePORTER application 10115597, Artemisinin activation in artemisinin resistant malarial parasites (5R21AI146506-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10115597. Licensed CC0.

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