Sl. no | Drug target | Functions in parasite | Refs. |
---|---|---|---|
1 | Acetyl CoA synthetase | It provides acetyl moieties for several metabolic and regulatory cellular pathways, which help in parasite growth | [42] |
2 | Adenylyl cyclase-β | It helps in cyclic adenosine monophosphate (cAMP) synthesis, an essential element of the parasite life cycle | [43] |
3 | Aminoacyl-tRNA synthetase | It helps in the protein synthesis (translation) process by adding an aminoacyl group to the 3’ end of tRNA | [44] |
4 | Aminopeptidase | It is a protease enzyme essential in cell maintenance, cell growth, peptide catabolism (during the asexual erythrocytic replication cycle), protein maturation, antigen presentation on immune cells, and hormone regulation | [15] |
5 | Anion-exchange protein-1 | Involved in erythrocyte invasion (adhesion of infected erythrocytes to endothelial cells) and acid-base homeostasis regulation | [15] |
6 | Apical membrane antigen-1 | Transmembrane protein. It helps parasites invade host erythrocytes | [15] |
7 | Aspartate aminotransferase | It is one of the key enzymes in energy metabolism and de novo biosynthesis of pyrimidines | [45] |
8 | Aspartate transcarbamoylase | It is essential in catalyzing the second step in de novo pyrimidine biosynthesis | [46] |
9 | ATP synthase | Involved in the ATP generation during aerobic glycolysis at the blood stage of the parasite’s life cycle | [47] |
10 | Calcium-dependent protein kinase-I | Significant role in activating translation of repressed mRNA during the sexual stage. It regulates parasite mobility. It helps in microneme secretion during erythrocyte invasion | [48] |
11 | Carbamoyl phosphate synthetase-II | It helps in the de novo pyrimidine biosynthesis process by catalyzing the formation of carbamoyl phosphate, glutamine, and ATP | [49] |
12 | Carbonic anhydrasU + 0065 | Metalloenzyme. An essential metabolic enzyme catalyzes carbon dioxide's reversible conversion to bicarbonate in pyrimidines de novo synthesis | |
13 | Casein kinase 2α | Involved in the critical cellular process; cell differentiation, proliferation, stress response, DNA damage, apoptosis, and circadian rhythm | [51] |
14 | cGMP-dependent protein kinase | Key regulator of cGMP signaling in the malaria parasite. It is required in the parasite life cycle's sexual and asexual stages | [52] |
15 | Choline transporter | The first enzyme of the Kennedy pathway. involved in the biosynthesis of phospholipid and phosphatidyl-choline | [53] |
16 | Choline phosphate cytidylyl transferase | It catalyzes the rate-limiting step of the Kennedy pathway and is crucial for the survival of the murine parasite | [54] |
17 | Cysteine protease | Key role in hemoglobin degradation and erythrocyte cytoskeletal proteins hydrolysis | |
18 | Cytochrome bc1 | Essential for pyrimidine biosynthesis | [47] |
19 | Cytochrome c oxidase (Complex IV) | Involved in Plasmodium mitochondrial electron transport chain | [56] |
20 | Dihydrofolate reductase | Involved in the pyrimidine synthesis in Plasmodium by de novo pathway | [57] |
21 | Dihydroorotate dehydrogenase | Involved in the de novo pyrimidine synthesis, the primary energy source and essential for parasite survival | [47] |
22 | Dihydropteroate synthase | Significant role in folate metabolism | [58] |
23 | Dipeptidyl aminopeptidase | Present in food vacuole and cleaves dipeptides from amino termini of proteins/oligopeptides | [59] |
24 | DNA methyltransferases | Involved in the epigenetic mechanism | [60] |
25 | DXP reductoisomerase | An essential enzyme of the DXP/MEP pathway that triggers isoprenoid formation (required for the production of cholesterol, dolichols, and ubiquinones) | [61] |
26 | Falcipain | Endopeptidase. It involves host hemoglobin hydrolysis, erythrocyte invasion, and erythrocyte rupture | [62] |
27 | Farnesyltransferase | Involved in the blood stage of the parasite life cycle | [63] |
28 | Fumarate hydratase | A vital component of the tricarboxylic acid cycle of the Plasmodium parasite (helps in the interconversion of fumarate to malate) | [47] |
29 | Gamma-glutamylcysteine synthetase | An essential enzyme of glutathione biosynthesis | [15] |
30 | Geranylgeranyl pyrophosphate synthase | Key branchpoint enzyme in isoprenoid biosynthesis | [43] |
31 | Glutathione reductase | A flavoenzyme regenerates glutathione (an essential enzyme antioxidant defense against cell damage) | [64] |
32 | Glutathione S-transferase | Involved in cellular detoxification | [65] |
33 | Glycerol 3-phosphate dehydrogenase | Key glycolytic homotetrameric enzyme. Involved in vesicular transport and apical organelle biogenesis | |
34 | Heat shock protein 90 | The most abundant chaperone in cells is responsible for cell cycle regulation and signal transduction | [68] |
35 | Hemozoin | A crystallized heme dimer. Sequestration of heme into hemozoin formation is an essential process for parasite development | [69] |
36 | Hexose transporter | Glucose uptake is mediated by the hexose transporter enzyme | [70] |
37 | Histone acetyltransferase | Involved in the acetylation of histone tails that causes localized chromatin relaxation and transcriptional activation of nearby genes | [71] |
38 | Histone acetyltransferase GCN5 | Key role in the epigenetic mechanism. It controls erythrocyte invasion and virulence in the Plasmodium parasite | [72] |
39 | Histone deacetylase | It catalyzes the deacetylation of acetylated histones leading to transcriptional repression | [71] |
40 | Hypoxanthine guanine phosphoribosyl transferase | Helps in DNA/RNA synthesis via de novo synthesis | [73] |
41 | Lactate dehydrogenase | The critical enzyme of energy production. It catalyzes the interconversion of pyruvate to lactate in the glycolysis process | [74] |
42 | Malate dehydrogenase | It involves NADH and citrate production to support the TCA cycle, ETC | [75] |
43 | Malatequinone oxidoreductase | Membrane protein. Involved in three essential pathways (ETC, TCA, and fumarate cycle) | [76] |
44 | Merozoite surface protein-1 | Essential for the attachment of merozoites to host receptor. Role in RBC invasion | [15] |
45 | Methionine aminopeptidase 1b | Metalloproteases. Involved in protein maturation and activation by catalyzing the removal of the N-terminal initiator methionine during protein synthesis | [77] |
46 | Mitogen-activated protein kinase 2 | It plays a vital role in critical cellular processes and signal transduction | [78] |
47 | N-myristoyl transferase | The key enzyme of post-translational modifications | [79] |
48 | NADH dehydrogenase type II | It is an essential enzyme of the Plasmodium mitochondrial electron transport chain system | [80] |
49 | Niemann-Pick Type C1 | Present on the parasite’s plasma membrane—essential protein for the intraerythrocytic growth of Plasmodium falciparum | [81] |
50 | Ornithine decarboxylase | Involvement in polyamines biosynthesis (key component of transcription, translation, and several cellular processes) | [82] |
51 | Orotatephospho-ribosyl transferase | Crucial enzyme for the de novo pyrimidine synthesis pathway | [83] |
52 | Orotidine 5′-monophosphate decarboxylase | The key enzyme for the de novo pyrimidine synthesis pathway | [84] |
53 | Orphan protein kinase PfPK7 | An essential enzyme in the melatonin transduction pathway | [85] |
54 | Pantothenic acid | Essential vitamin and precursor of coenzyme A | [86] |
55 | Phosphocholine cytidylyltransferase | Essential enzyme for the biosynthesis of phosphatidylcholine | [54] |
56 | Phosphodiesterase β | The key enzyme for developing the asexual blood stage of the malaria parasite | [87] |
57 | Phosphoinositide lipid kinases | Lipid phosphoinositides are signaling molecules involved in cellular functions (e.g. cell growth, cell division, and membrane trafficking) | [88] |
58 | Phosphatidylinositol 3-phosphate | An essential enzyme in vesicular trafficking processes and intraerythrocytic development | [89] |
59 | Phosphoribosyl transferase | Key purine salvage enzyme | [90] |
60 | Plasmepsin | Plasmepsin is responsible for hemoglobin digestion, cytoskeleton protein processing, oocyst development, parasite virulence modulation, and host-targeted protein export | [91] |
61 | Reactive oxygen species | It plays a significant role in the regulatory mediators in signaling processes (e.g. lipid peroxidation, cell signaling, ETC, and hemoglobin digestion) | [92] |
62 | Rhoptry-associated protein | Involve in the invasion of RBC by merozoites | [93] |
63 | S-adenosylhomo-cysteine hydrolase | It is required for the metabolic pathway (sulfur-containing amino acids) and biological methylation process | [94] |
64 | Serine repeat antigen-5 | The key enzyme for parasite development at the blood stage | [95] |
65 | Serine/threonine-protein kinase | Involved in cellular processes such as differentiation, proliferation, cell cycle progression, apoptosis, and DNA damage | [96] |
66 | Signal peptide peptidase | Membrane-bound endopeptidases. Help in parasite protein maturation and transport | [97] |
67 | Subtilisin-like protease-1 | Role in merozoite invasion and mediates the proteolytic maturation | [98] |
68 | Succinate dehydrogenase Complex II | Essential enzyme for the TCA, ETC pathway | [99] |
69 | SUMOylation | A post-translational modification enzyme in the parasite life cycle | [100] |
70 | Surface anion channel | Parasite-induced ion channel on host erythrocyte membrane mediates nutrients update, various bulky organic solutes, and supports intracellular parasite growth | [101] |
71 | Thioredoxin reductase | Homo dimeric protein. It maintains redox equilibrium in the glutathione system | [102] |
72 | Thymidylate synthase | Involved in folate de novo synthesis | [103] |
73 | Topoisomerase | Role in DNA transcription, replication, repair, and cell division | [104] |
74 | V-Type H + ATPase | Regulate intracellular pH and plasma membrane potential. It is associated with chloride channels | [105] |