Subtilisin-like Serine Protease 1 (SUB1) as an Emerging Antimalarial Drug Target: Current Achievements in Inhibitor Discovery Miniperspective

Widespread resistance to many antimalarial therapies currently in use stresses the need for the discovery of new classes of drugs with new modes of action. The subtilisin-like serine protease SUB1 controls egress of malaria parasites (merozoites) from the parasite-infected red blood cell. As such, SUB1 is considered a prospective target for drugs designed to interrupt the asexual blood stage life cycle of the malaria parasite. Inhibitors of SUB1 have potential as wide-spectrum antimalarial drugs, as a single orthologue of SUB1 is found in the genomes of all known Plasmodium species. This mini-perspective provides a short overview of the function and structure of SUB1 and summarizes all of the published SUB1 inhibitors. The inhibitors are classified by the methods of their discovery, including both rational design and screening.

Automated summary

The widespread resistance to current antimalarial therapies highlights the need for new classes of drugs with different mechanisms of action. The subtilisin-like serine protease SUB1 is a potential target for drugs aimed at disrupting the asexual blood stage of the malaria parasite. This mini-perspective provides an overview of SUB1's function and structure, and summarizes the published inhibitors of SUB1, which were discovered using both rational design and screening methods.