DZIF Boromycin

Boromycin as a new antimalarial multitarget candidate with pronounced gametocytocidal activity

01/12/2026 to 30/11/2029

Malaria continues to pose a significant burden on populations in endemic areas, especially in Sub-Saharan Africa. Artemisinin combination therapies (ACTs) are the current mainstay treatments of P. falciparum malaria. While ACTs remain efficacious in most malaria endemic areas, they exclusively target the asexual stages of the parasite, leaving the mature sexual stages unaffected. As a result, transmission of the parasite can still occur even after successful treatment. Moreover, the recurring emergence of drug-resistant parasite strains presents a critical obstacle to malaria control and eradication efforts. The recent identification of P. falciparum strains in Africa with partial resistance to artemisinin represents a major threat to the most vulnerable populations and underscores the urgency of developing new therapeutic strategies.
Boromycin, a boron-containing antibiotic produced by Streptomyces antibioticus, has been described as a potent antimicrobial compound. Recently, boromycin was found to be a potent, multi-stage antimalarial candidate. The compound showed activity against the asexual stages of P. falciparum (both sensitive and resistant strains) and P. knowlesi, as well as against mature gametocytes, at low nanomolar concentrations. Notably, boromycin displays a rapid onset of action comparable to pyrimethamine and remains effective against artemisinin-resistant strains. Its excellent selectivity index further supports its potential as a safe and efficacious antimalarial agent. Overall, boromycin shows promising antimalarial activity and demonstrates significant potential for transmission blocking.
The overarching aim of this proposal is to advance boromycin as a next-generation antimalarial drug candidate. Specifically, we will (1) evaluate its pharmacokinetics, safety, metabolism, and toxicity in preclinical models (2) further characterize its antimalarial activity across the parasite’s life cycle in vitro and in vivo; and (3) enable sustainable production by optimizing fermentation conditions, synthesizing tool compounds, and identifying the biosynthetic gene cluster (BGC) to uncover the biosynthetic pathway and enhance yields via metabolic engineering. This integrated approach will pave the way for future clinical development and support the long-term goal of malaria eradication.