Expression of The Fab Enzymes (Fab I And Fab Z) From Plasmodium Falciparum After Exposure To Artemisia Afra Plant Extracts And Drugs Screening

Abstract

Background:The emergence and spread of drug resistance of the malaria parasite to the main treatment emphasis the need to develop new antimalarial drugs. In this context, the fatty acid biosynthesis (FAS_II) pathway of the malaria parasite is one of the ideal target due to its crucial role in parasite survival.Method:We report in this study the expression and the affinity binding of two Fab enzymes (FabI and FabZ) after exposure of the parasite using different extracts of the Artemisia afra and after a virtual screening with the different plant compounds. Two differents strains of Plasmodium falciparum was used: W2 (CQ_resistant) and D6 (CQ_sensitive) with a parasiteamia of 4%. The parasites were exposed during 2 days to different Artemisia afra extracts . Gene expression was done to determine the level of expression of the fab enzymes after treatments. A GCMS was run to determine the different compounds of the plant extracts following by a virtual screening between the fab enzymes and the active compounds using Pyrex. Result:The results showed different expression patterns of the Fab enzymes. FabI was downregulated in the W2 and D6 strains by the ethanolic extract in a higher rate for W2. Hexane and DCM extracts increased the production of FabI respectively in W2 and D6 strains. A different expression pattern was observed for Fab Z. The expression of FabZ in the W2 strain were all upregulated. The enzyme was downregulated only in the D6 strain when exposed to the ethanolic and hexane extracts of the plant. After virtual screening, a lot of compounds were found to interact with the two fab enzymes. Hits compounds for FabI and FabZ with high biding energy were detected. 11alpha-Hydroxyprogesterone and Aspidospermidin-17-ol were found to have high binding energy with FabI respectively (-10.7 kcal/mol; -10.2kcal/mol). Fab Z was having also a high affinity with the two following hits compounds: 11alpha-Hydroxyprogesterone (-10 kcal/mol) and Thiourea (-8.4 Kcal/mol). Conclusion:The study showed that Artemisia afra is a big source of antimalarial drugs, and could act not only as a curative but also as prophylactic due to its effects on the Fab enzymes.