Description
- Abstract:
- Plasmodium falciparum malaria is one of the leading causes of death among children worldwide, killing more than 500,000 sub-Saharan African children annually. Increasing resistance to artemisinin, the standard of care for severe malaria (SM), underscores the need to identify novel anti-malarial therapeutics. Recent work has identified that the P. falciparum Glutamic Acid Rich Protein (PfGARP) antigen is uniquely targeted by the immune systems of children resistant to severe malaria, suggesting that Anti-PfGARP antibodies may confer protection against SM. Anti-PfGARP human antibodies kill up to 99% of P. falciparum parasites in culture. Through an antibody-inhibition binding screening, we identified drug 2741-19 as a small molecule with significant competitive inhibition of PfGARP-anti-PfGARP binding. This suggests that our drug exhibits high affinity binding to PfGARP and could mimic the activity of Anti-PfGARP Abs. To characterize the anti-malaria effects of drug 2741-19 against in vitro parasites, we conducted growth inhibition assays using P. falciparum wild-type parasites and PfGARP-KO parasites. In our assays, we found that drug 2741-19 kills parasites with an IC50 = 205.6 nM (Figure 1), but comparable killing is also seen in our PfGARP-knock-out model of P. falciparum (IC50 = 295 nM, Figure 2). Our results suggest drug 2741-19 reduces parasitemia by killing parasites through an elusive mechanism that may be independent of PfGARP or may involve two distinct binding targets. Therefore, this drug represents a promising novel anti-malarial therapeutic for treating or preventing severe malaria, particularly against drug-resistant strains.
- Notes:
- Scholarly concentration: Non-Scholarly Concentrator
Access Conditions
- Use and Reproduction
- All rights reserved
- Rights
- In Copyright
- Restrictions on Use
- All Rights Reserved
Citation
Maguire, S., Ardito, A., Najrana, T., et al.,
"Drug 2741-19 is a Novel Therapeutic Candidate for Treating Severe Malaria"
(2025).
Warren Alpert Medical School Academic Symposium.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:sq826bce/
Relations
Collection:
-
Warren Alpert Medical School Academic Symposium
The Warren Alpert Medical School Academic Symposium is an annual event at Warren Alpert Medical School of Brown University that provides Year II medical students a venue to present their summer research in a poster format. Participation in the Symposium …...