Table 2 |.

Antimalarial targets with in vivo validation

Target (systematic name)	Mechanism of action	Noteworthy inhibitors	Refs.
Plasmepsins IX and X; PMIX, PMX (PF3D7_1430200, PF3D7_0808200)	Aspartic proteases that regulate the maturation of enzymes required to disrupt host cell membranes during parasite egress	WM382	77,201–203
Serine hydroxymethyltransferase; SHM (PF3D7_1456100)	Converts serine to glycine	-	204
Glycylpeptide N-tetradecanoyltransferase; NMT (PF3D7_1412800)	Transfers myristate to the N-terminal glycine of several protein molecules	IMP-1002	205,206
Lysyl tRNA synthetase; KRS (PF3D7_1350100)	ATP-dependent enzyme that catalyzes charging the tRNA synthetase with lysine; essential for protein biosynthesis	-	101
Acyl-CoA synthetases; ACS10/11 (PF3D7_0525100, PF3D7_1238800)	Coenzymes predicted to be involved in the synthesis of long-chain fatty acids	GSK701	92,207,208
Acetyl-CoA synthetase; AcAS (PF3D7_0627800)	Involved in the synthesis of acetyl-CoA	MMV019721, MMV084978	91
Cyclin-dependent-like kinase 3; CLK3 (PF3D7_1114700)	Kinase involved in mRNA splicing; inhibition results in lethal defects in mRNA processing	TCMDC-135051	114
cGMP-dependent protein kinase; PKG (PF3D7_1436600)	Involved in cyclic GMP signalling; an essential protein	MMV030084	94
Tyrosine tRNA synthetase; YRS (PF3D7_1117500)	ATP-dependent enzyme that catalyzes charging tRNA synthetase with tyrosine; essential for protein biosynthesis	ML901	105
Phenylalanine tRNA synthetase; FRS (PF3D7_0109800)	Catalyzes charging tRNA synthetase with phenylalanine	BRD5018	209
Threonine tRNA synthetase; TRS (PF3D7_1126000)	Catalyzes charging tRNA synthetase with threonine; essential for protein biosynthesis	Borrelidin	210
Histone deacetylase 1; HDAC1 (PF3D7_0925700)	Removes acetyl groups from histones	JF363, JX35	211–213
Proteasome (including PF3D7_1011400)	A multisubunit protein complex that drives protein degradation	Vinyl sulfones, epoxyketones, macrocyclic peptides, asparagine ethylenediamines	76,117,119,122,214,215