New leads for drug repurposing against malaria

Area of Science:

• Drug discovery and development
• Parasitology
• Pharmacology

Background:

• Artemisinin-based combination therapies (ACTs) are frontline malaria treatments.
• Drug resistance to ACTs is driving a resurgence of malaria globally.
• Novel antimalarial strategies are urgently needed.

Purpose of the Study:

• To identify existing US Food and Drug Administration (FDA)-approved over-the-counter (OTC) drugs that can be repurposed for malaria treatment.
• To analyze drug efficacy against Plasmodium falciparum and Plasmodium berghei.
• To discover potential next-generation antimalarial drug leads.

Main Methods:

• Growth inhibition assays were performed on Plasmodium falciparum and Plasmodium berghei.
• Data from 226 FDA-approved drugs (189 for P. falciparum, 37 for P. berghei) were analyzed.
• Drug candidates were evaluated for their potential as antimalarials.

Main Results:

• Eighteen currently used drugs demonstrated suitability for further development as antimalarials.
• Eight identified drugs share enzymatic targets with the human host and the malaria parasite.
• These shared targets offer a basis for mechanistic and drug selectivity studies.

Conclusions:

• Repurposing FDA-approved OTC drugs presents a viable strategy to combat drug-resistant malaria.
• The identified drug candidates, particularly those with shared targets, are promising leads for next-generation antimalarials.
• Further research into these drugs can accelerate the development of new malaria treatments.