# Development of a Synergistic Drug Combination for Prevention and Treatment of Malaria

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $572,593

## Abstract

Project Summary
 Drugs targeting the liver stage offer many advantages over drugs that merely target the blood stage. First,
drugs active against the liver stage represent true causally prophylactic agents that can prevent all disease
symptoms, including death, associated with malaria. Secondly, it has been established that while wild-caught
mosquitoes may harbor thousands of sporozoites, only ≈10 sporozoites are transferred in a single bite to the
human host. Over the next 2-3 weeks the sporozoite reproduces in the liver to produce 10,000-30,000
descendants before the schizont ruptures and parasites flood into the bloodstream where the absolute parasite
burden may increase to ten thousand billion (1013) circulating plasmodia. Clearly it is advantageous to strike at
the liver stage where parasite numbers are low, to diminish the likelihood of selecting for a drug resistant mutant
and before the infection has a chance to weaken the defenses of the human host. Our primary goal in this project
is to develop a drug combination that is active against P. falciparum, causative agent of the most virulent, often
fatal form of malaria. The drug combination will act synergistically while targeting the parasite in the liver, blood
and also the vector stages that are critical for disease transmission. Studies (by us and others) have shown that
ELQ-300 targets all 3 of these life cycle stages. The ultimate objective of our proposed work is the development
of an inexpensive ELQ-300 prodrug that can be co-formulated with other antimalarials in a synergistic
combination to prevent and treat malaria and support the worldwide effort to control and eradicate the disease.
This study focuses on the combination of ELQ-300 prodrugs with biguanides including proguanil. We seek a
better understanding of the biochemical mechanism that underlies the antimalarial synergism that exists between
ELQ-300 and biguanides. A better understanding of this interaction will help to design a biguanide/ELQ-300
prodrug combination that is safe for use in humans for weekly prophylaxis and treatment of malaria.

## Key facts

- **NIH application ID:** 9829034
- **Project number:** 5R01AI100569-07
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Michael Kevin RISCOE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $572,593
- **Award type:** 5
- **Project period:** 2012-07-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9829034

## Citation

> US National Institutes of Health, RePORTER application 9829034, Development of a Synergistic Drug Combination for Prevention and Treatment of Malaria (5R01AI100569-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9829034. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*