Table 3 |.
Antimalarial targets with in vitro validation
| Target (systematic name) | Mechanism of action | Noteworthy inhibitors | Refs. |
|---|---|---|---|
| Farnesyl pyrophosphate–geranylgeranyl diphosphate synthase; FPPS–GGPPS (PF3D7_1128400) | Dual-function enzyme involved in prenylation of C15 and C20 chains | MMV019313 | 216–221 |
| Niemann–Pick type C1-related protein; NCR1 (PF3D7_0107500) | Transports lipophilic substrates and recycles sphingolipids; essential for maintaining the membrane lipid composition of blood-stage parasites | – | 222 |
| GCN5 (PF3D7_0823300) | Histone acetyltransferase | - | 223 |
| Dephospho-CoA kinase; DPCK (PF3D7_1443700) | Required for coenzyme A synthesis in the apicoplast | - | 207,224,225 |
| Adenylyl cyclase-β; ACβ (PF3D7_0802600) | Synthesizes the second messenger cAMP | - | 226 |
| Hexose transporter 1; HT1 (PF3D7_0204700) | Transports essential hexose across the parasite plasma membrane | - | 227 |
| cGMP-specific 3′,5′-cyclic phosphodiesterase-δ; PDE (PF3D7_1470500) | Expressed by mature gametocytes and regulates erythrocytic mechanical properties | Tadalafil | 228 |
| 2-C-methyl-d-erythritol 4-phosphate cytidylyl; IspD (PF3D7_0106900) | Acts in the methylerythritol phosphate pathway, which synthesizes the essential isoprenoid precursors isopentenyl diphosphate and dimethylallyl diphosphate | MMV008138 | 229,230 |
| Formate-nitrite transporter; FNT (PF3D7_0316600) | A high-capacity lactate-proton symporter | - | 231–235 |
| Hypoxanthine-guanine phosphoribosyltransferase; HGXPRT (PF3D7_1012400) | Essential enzyme in the purine salvage pathway | - | 236 |
| Purine nucleoside phosphorylase; PNP (PF3D7_0513300) | Essential enzyme in the purine salvage pathway | - | 115 |
| Malate:quinone oxidoreductase; MQO (PF3D7_0616800) | Essential enzyme in mitochondrial electron transport, the tricarboxylic acid cycle and the fumarate cycle | - | 237 |
| CPSF (PF3D7_0513200) | Regulates mRNA polyadenylation | AN3661 | 238 |
| Monoacylglycerol lipase; MAGL (PF3D7_1038900) | Mediates hydrolysis of lipid esters, including a MAGL acylglycerol substrate | Salinopostin A | 239 |
| Leucine–tRNA ligase; LRS (PF3D7_0622800) | Essential enzyme that catalyzes charging tRNA synthetase with phenylalanine | Benzoxaboroles | 104 |
| Isoleucine–tRNA ligase; cIRS (PF3D7_1332900) | Essential enzyme in blood and liver stages | Thienopyrimidines | 106 |