Potential antimalarial compound discovered in institute's microbe collection

Scientists at The Herbert Wertheim UF Scripps Institute of Biomedical Innovation & Technology may have discovered a new antimalarial compound within their extensive natural compound collection. Malaria, a deadly infectious disease affecting approximately 280 million people each year, disproportionately kills small children and is becoming more resistant to standard treatments.

The researchers, led by chemist Ben Shen, Ph.D., discovered several compounds within bacteria extracts housed in the collection. These compounds demonstrated the ability to rapidly kill malaria parasites at all stages of their life cycle, unlike existing antimalarial drugs. Co-first author Chantal Bader, Ph.D., explained that the team systematically screened a subset of the 122,550-strain collection, seeking previously unexplored compounds.

The researchers initially screened 81 purified natural compounds, revealing six promising candidates. They then expanded their search to 1,531 samples created by Actinobacteria, finding that about 20% had antimalarial properties. After filtering out toxic compounds to humans, they studied the top candidates' chemical composition and activity, discovering several novel compounds named SPAs, short for sphaeriaurantins.

Testing showed that the most active SPA compound cleared 99.9% of the multidrug-resistant malaria parasite, Plasmodium falciparum, from blood and cultured liver cells, indicating its effectiveness at multiple stages of the parasite's life cycle. The researchers noted that the SPAs are unlikely to develop drug resistance. Their findings were published in the Journal of the American Chemical Society in August.

The next steps involve characterizing the pharmacological and therapeutic potential of the SPA scaffold, including identifying its primary molecular target and understanding its mechanism of action. The Natural Products Discovery Center at The Wertheim UF Scripps Institute houses a vast collection of microbes and their extracts, assembled over 80 years ago.

This collection, unique due to international treaties on genetic sovereignty, has been instrumental in the discovery of important medicines such as penicillin and rapamycin. The researchers aim to continue mining this genetic wealth for the benefit of humanity and to preserve the irreplaceable value of natural product biodiversity.