Malaria remains a major health hazard for humans, despite the availability of efficacious antimalarial drugs and other interventions. Given that the disease is often deadly for children under 5 years and pregnant women living in malaria-endemic areas, an efficacious vaccine to prevent transmission and clinical disease would be ideal. Plasmodium, the causative agent of malaria, uses proteases and protease inhibitors to control and process to invade host, modulate host immunity, and for pathogenesis. Plasmodium parasites rely on these proteases for their development and survival, including feeding their metabolic needs and invasion of both mosquito and human tissues, and have thus been explored as potential targets for prophylaxis. In this chapter, we have discussed the potential of proteases like ROM4, SUB2, SERA4, SERA5, and others as vaccine candidates. We have also discussed the role of some protease inhibitors of plasmodium and mosquito origin. Inhibition of plasmodium proteases can interrupt the parasite development at many different stages therefore understanding their function is key to developing new drugs and malaria vaccines.

• Klíčová slova
• Antimalarial drugs, Plasmodium, Protease inhibitors, Proteases, Serpins, Vaccine development, Vaccines, Vector-borne pathogens,
• MeSH
• inhibitory proteas farmakologie   terapeutické užití   MeSH
• lidé MeSH
• malárie farmakoterapie   imunologie   parazitologie   prevence a kontrola   MeSH
• Plasmodium * účinky léků   enzymologie   imunologie   fyziologie   MeSH
• proteasy * imunologie   MeSH
• protozoální proteiny * antagonisté a inhibitory   imunologie   MeSH
• vakcína proti malárii * imunologie   MeSH
• vývoj vakcíny MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inhibitory proteas MeSH
• proteasy * MeSH
• protozoální proteiny * MeSH
• vakcína proti malárii * MeSH

Malaria is a disease caused by protozoan parasites of the genus Plasmodium that affects millions of people worldwide. In recent years there have been parasite resistances to several drugs, including the first-line antimalarial treatment. With the aim of proposing new drugs candidates for the treatment of disease, Quantitative Structure⁻Activity Relationship (QSAR) methodology was applied to 83 N-myristoyltransferase inhibitors, synthesized by Leatherbarrow et al. The QSAR models were developed using 63 compounds, the training set, and externally validated using 20 compounds, the test set. Ten different alignments for the two test sets were tested and the models were generated by the technique that combines genetic algorithms and partial least squares. The best model shows r² = 0.757, q²adjusted = 0.634, R²pred = 0.746, R²m = 0.716, ∆R²m = 0.133, R²p = 0.609, and R²r = 0.110. This work suggested a good correlation with the experimental results and allows the design of new potent N-myristoyltransferase inhibitors.

• Klíčová slova
• N-myristoyltransferase, QSAR, drug development, malaria, mosquito-borne protozoal infection,
• MeSH
• acyltransferasy antagonisté a inhibitory   MeSH
• algoritmy MeSH
• antimalarika chemie   farmakologie   MeSH
• kvantitativní vztahy mezi strukturou a aktivitou MeSH
• léková rezistence účinky léků   MeSH
• lidé MeSH
• metoda nejmenších čtverců MeSH
• molekulární modely MeSH
• Plasmodium účinky léků   enzymologie   MeSH
• protozoální proteiny antagonisté a inhibitory   MeSH
• racionální návrh léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acyltransferasy MeSH
• antimalarika MeSH
• glycylpeptide N-tetradecanoyltransferase MeSH Prohlížeč
• protozoální proteiny MeSH