Parasite and host kinases as targets for antimalarials

Area of Science:

• Malariology
• Medicinal Chemistry
• Parasitology

Background:

• Global malaria burden has decreased but is now reversing due to drug resistance.
• Artemisinin-based combination therapies and transmission control measures have been effective but face challenges.
• Emerging resistance to antimalarial treatments necessitates the development of novel therapeutic agents.

Approach:

• Protein kinases are attractive antimalarial drug targets due to their druggability in other diseases.
• Kinase-focused antimalarial drug discovery benefits from existing scaffolds, inhibitor libraries, and assays.
• This review overviews validated Plasmodium kinase targets, inhibitors, and host cell kinase potential for host-directed therapy.

Key Points:

• Diversification of Plasmodium kinase targets is crucial, as current efforts focus on a limited number.
• Polypharmacology, using kinase inhibitors, is a viable strategy to limit drug resistance.
• Host-directed therapy and targeting sexual stage-specific kinases can preempt resistance and block transmission.

Conclusions:

• Developing new antimalarial drugs targeting untapped Plasmodium kinase targets is essential.
• Strategies include exploring polypharmacology and host-directed therapies to overcome resistance.
• Targeting kinases offers a promising avenue for future malaria control and elimination efforts.