# Evaluating host-directed therapeutics against blood-stage malaria parasites

> **NIH NIH R21** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2022 · $199,375

## Abstract

Summary
Malaria remains a major global health problem, causing tremendous morbidity and mortality. Disease occurs
during the blood-stage of human infections with asexual proliferation of Plasmodium parasites in red blood cells
(RBCs) leading to their destruction. Due to the evolving threat of drug resistance, there is an urgent need to
develop new antimalarials for control and eradication efforts. We hypothesize that host-directed inhibitors (HDIs)
will circumvent drug resistance in the parasite, which would have to significantly alter its biology to bypass its
requirement for the essential host target. An increasing number of studies have reported RBC-specific inhibitors,
but these are poorly validated. We propose to identify and validate HDIs. We will include compounds identified
by screening a large drug repurposing library with putative targets in the RBC proteome. To validate host
targeting as the antimalarial mechanism of action, we will perform synthetic lethal assays using in vitro cultured
RBCs (cRBCs) with knockdown of putative targets. Cellular Thermal Shift Assays will be used to demonstrate
direct binding to host targets. Finally, for compounds that appear to be bona fide HDIs, we will assess the ability
of the parasite to develop resistance. The establishment of a pipeline to validate host targeting as the mechanism
of action of putative HDIs will be a significant advance to the field, supporting the development of host-directed
therapeutics in the future.

## Key facts

- **NIH application ID:** 10528133
- **Project number:** 1R21AI166478-01A1
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** Manoj T Duraisingh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $199,375
- **Award type:** 1
- **Project period:** 2022-07-14 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10528133

## Citation

> US National Institutes of Health, RePORTER application 10528133, Evaluating host-directed therapeutics against blood-stage malaria parasites (1R21AI166478-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10528133. Licensed CC0.

---

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