Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)

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Parasite Lifecycle Stages
Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)

Stage ID:	1
Name:	Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)
Associated with:	12 targets
	23 ligands

Description
The collective lifecycle stage that occurs in the liver of the host organism and can include: sporozoite, the motile form of the parasite that is responsible for the initial infection of the host. Sporozoites from the salivary glands of the vector (female Anopheles mosquitos) are injected into the host during the mosquito's blood meal, before migrating to the host liver and entering hepatic cells. The number of sporozoites introduced during a blood meal is low (<100) and the process of hepatocyte infection is rapid (<1 hour). hepatic schizont, the multinucleate form of the parasite that develops in hepatic cells from the sporozoite by asexual reproduction (schizogony) with incomplete cytokineses. This form of the parasite is also found in host erythrocytes (see erythrocytic schizont). hepatic merozoite, completion of cytokinesis produces several thousand merozoites from a single schizont, leading to rupture of the infected hepatocyte and release of merozoites into the bloodstream. These merozoites do not re-enter hepatocytes but invade erythrocytes instead and this begins the asexual blood stage (see Plasmodium asexual blood stage). Merozoites are non-motile but have an apical complex that facilitates entry into host cells. This form of the parasite is also found in host erythrocytes (see erythrocytic merozoite). Further development of the Plasmodium infection can be prevented by blocking the parasite lifecycle during an early point of the liver stage. Antimalarial drugs that have liver stage activity have the potential to hit new targets that are not present or essential during the asexual blood stage. It has also been suggested that resistance to these compounds may develop more slowly due to the much smaller number of parasites present during this initial stage of the disease.

Description

The collective lifecycle stage that occurs in the liver of the host organism and can include:

sporozoite, the motile form of the parasite that is responsible for the initial infection of the host. Sporozoites from the salivary glands of the vector (female Anopheles mosquitos) are injected into the host during the mosquito's blood meal, before migrating to the host liver and entering hepatic cells. The number of sporozoites introduced during a blood meal is low (<100) and the process of hepatocyte infection is rapid (<1 hour).
hepatic schizont, the multinucleate form of the parasite that develops in hepatic cells from the sporozoite by asexual reproduction (schizogony) with incomplete cytokineses. This form of the parasite is also found in host erythrocytes (see erythrocytic schizont).
hepatic merozoite, completion of cytokinesis produces several thousand merozoites from a single schizont, leading to rupture of the infected hepatocyte and release of merozoites into the bloodstream. These merozoites do not re-enter hepatocytes but invade erythrocytes instead and this begins the asexual blood stage (see Plasmodium asexual blood stage). Merozoites are non-motile but have an apical complex that facilitates entry into host cells. This form of the parasite is also found in host erythrocytes (see erythrocytic merozoite).

Further development of the Plasmodium infection can be prevented by blocking the parasite lifecycle during an early point of the liver stage. Antimalarial drugs that have liver stage activity have the potential to hit new targets that are not present or essential during the asexual blood stage. It has also been suggested that resistance to these compounds may develop more slowly due to the much smaller number of parasites present during this initial stage of the disease.

Interactions

Key to terms and symbols

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Target	Ligand		Sp.	Action	Value	Parameter	Reference
Plasmodium falciparum dihydroorotate dehydrogenase	DSM705		Pb Plasmodium berghei P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Pb is used in rodent model studies of malaria. ✖	-	7.9	pEC₅₀	13
Plasmodium falciparum dihydroorotate dehydrogenase	DSM705	pEC₅₀ 7.9 (EC₅₀ 1.3x10^-8 M) Luciferase bioluminescence (Pbluc) assay to measure sporozoite invasion into HepG2 liver cells (prophylactic activity) [13] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum phenylalanyl-tRNA synthetase alpha subunit	BRD3444		Pb Plasmodium berghei P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Pb is used in rodent model studies of malaria. ✖	-	6.8	pEC₅₀	9
	BRD3444	pEC₅₀ 6.8 (EC₅₀ 1.4x10^-7 M) Luciferase bioluminescence assay to measure parasite invasion into HepG2 liver cells [9] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum phenylalanyl-tRNA synthetase alpha subunit	BRD7929		Pb Plasmodium berghei P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Pb is used in rodent model studies of malaria. ✖	-	6.8	pEC₅₀	9
	BRD7929	pEC₅₀ 6.8 (EC₅₀ 1.62x10^-7 M) Luciferase bioluminescence assay to measure parasite invasion into HepG2 liver cells [9] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum N-myristoyltransferase	compound 34c [PMID: 24641010]		Pb Plasmodium berghei P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Pb is used in rodent model studies of malaria. ✖	-	6.4	pEC₅₀	15
Plasmodium falciparum N-myristoyltransferase	compound 34c [PMID: 24641010]	pEC₅₀ 6.4 (EC₅₀ 3.72x10^-7 M) Luciferase bioluminescence assay to measure viability of exoerythrocytic forms (EEF) [15] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum phosphatidylinositol 4-kinase beta	MMV048		Pc Plasmodium cynomolgi P. cynomolgi (Pc) is a malaria parasite that infects non-human primate species with the natural mammalian host being Asian Old World monkeys. Pc is used as a model for human P. vivax infection because these species are phylogenetically close and share a similar lifecycle, including the dormant liver form (hypnozoite). ✖	-	7.2	pIC₅₀	14
Plasmodium falciparum phosphatidylinositol 4-kinase beta	MMV048	pIC₅₀ 7.2 (IC₅₀ 6.4x10^-8 M) P. cynomolgi assay to assess inhibition of liver stage development (prophylactic activity) [14] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum phosphatidylinositol 4-kinase beta	UCT943		Pc Plasmodium cynomolgi P. cynomolgi (Pc) is a malaria parasite that infects non-human primate species with the natural mammalian host being Asian Old World monkeys. Pc is used as a model for human P. vivax infection because these species are phylogenetically close and share a similar lifecycle, including the dormant liver form (hypnozoite). ✖	-	>8.0	pIC₅₀	4
Plasmodium falciparum phosphatidylinositol 4-kinase beta	UCT943	pIC₅₀ >8.0 (IC₅₀ <1x10^-8 M) P. cynomolgi assay to assess inhibition of liver stage development (prophylactic activity) [4] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum phosphatidylinositol 4-kinase beta	UCT943		Pb Plasmodium berghei P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Pb is used in rodent model studies of malaria. ✖	-	9.0	pIC₅₀	4
Plasmodium falciparum phosphatidylinositol 4-kinase beta	UCT943	pIC₅₀ 9.0 (IC₅₀ 9.2x10^-10 M) Luciferase bioluminescence assay to measure sporozoite invasion (prophylactic activity) [4] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum phosphatidylinositol 4-kinase beta	KDU691		Py Plasmodium yoelii P. yoelii (Py) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Py is used in rodent model studies of malaria, in particular the immune response and in vaccine development. ✖	-	7.4	pIC₅₀	11
Plasmodium falciparum phosphatidylinositol 4-kinase beta	KDU691	pIC₅₀ 7.4 (IC₅₀ 3.6x10^-8 M) Sporozoite hepatocyte invasion assay [11] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum elongation factor 2	M5717		Pb Plasmodium berghei P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Pb is used in rodent model studies of malaria. ✖	-	8.8	pEC₅₀	3
Plasmodium falciparum elongation factor 2	M5717	pEC₅₀ 8.8 (EC₅₀ 1.65x10^-9 M) P. berghei Luciferase liver stage assay [3] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase	P218		Pf Plasmodium falciparum P. falciparum (Pf) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pf is responsible for the majority of malaria related deaths and is the most prevalent species in sub-Saharan Africa. ✖	-	>7.9	pEC₅₀	16
	P218	pEC₅₀ >7.9 (EC₅₀ <1.2x10^-8 M) Primary human hepatocyte assay to assess inhibition of hepatic schizonts (prophylactic activity) [16] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase	P218		Pv Plasmodium vivax P. vivax (Pv) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pv is the second most common cause of malaria in humans, after P. falciparum, and is prevalent in Southeast Asia and Latin America. Pv has a dormant liver stage that can reactivate and lead to clinical symptoms. ✖	-	7.3	pEC₅₀	16
	P218	pEC₅₀ 7.3 (EC₅₀ 4.5x10^-8 M) Primary human hepatocyte assay to assess inhibition of hepatic schizonts (prophylactic activity) [16] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum cGMP-dependent protein kinase	MMV030084		Pb Plasmodium berghei P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Pb is used in rodent model studies of malaria. ✖	-	6.7	pIC₅₀	17
Plasmodium falciparum cGMP-dependent protein kinase	MMV030084	pIC₅₀ 6.7 (IC₅₀ 1.99x10^-7 M) Luciferase bioluminescence assay to measure sporozoite invasion into HepG2 liver cells (prophylactic activity) [17] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum prolyl-tRNA synthetase	halofuginone		Pb Plasmodium berghei P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Pb is used in rodent model studies of malaria. ✖	-	7.8	pIC₅₀	5
Plasmodium falciparum prolyl-tRNA synthetase	halofuginone	pIC₅₀ 7.8 (IC₅₀ 1.7x10^-8 M) [5] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum lysyl-tRNA synthetase	cladosporin		Py Plasmodium yoelii P. yoelii (Py) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Py is used in rodent model studies of malaria, in particular the immune response and in vaccine development. ✖	-	7.4	pIC₅₀	8
Plasmodium falciparum lysyl-tRNA synthetase	cladosporin	pIC₅₀ 7.4 (IC₅₀ 3.91x10^-8 M) Sporozoite hepatocyte invasion assay [8] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum lysyl-tRNA synthetase	compound 5 [PMID: 30894487]		Pv Plasmodium vivax P. vivax (Pv) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pv is the second most common cause of malaria in humans, after P. falciparum, and is prevalent in Southeast Asia and Latin America. Pv has a dormant liver stage that can reactivate and lead to clinical symptoms. ✖	-	6.0	pEC₅₀	2
Plasmodium falciparum lysyl-tRNA synthetase	compound 5 [PMID: 30894487]	pEC₅₀ 6.0 (EC₅₀ 9.5x10^-7 M) [2] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum histone deacetylase 1	compound 1u [PMID: 30245402]		Pb Plasmodium berghei P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Pb is used in rodent model studies of malaria. ✖	-	7.6	pIC₅₀	6
Plasmodium falciparum histone deacetylase 1	compound 1u [PMID: 30245402]	pIC₅₀ 7.6 (IC₅₀ 2.5x10^-8 M) P. berghei Luciferase liver stage assay [6] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum cytochrome b	ELQ-300		Pc Plasmodium cynomolgi P. cynomolgi (Pc) is a malaria parasite that infects non-human primate species with the natural mammalian host being Asian Old World monkeys. Pc is used as a model for human P. vivax infection because these species are phylogenetically close and share a similar lifecycle, including the dormant liver form (hypnozoite). ✖	-	~7.0	pIC₅₀	12
Plasmodium falciparum cytochrome b	ELQ-300	pIC₅₀ ~7.0 (IC₅₀ ~1x10^-7 M) High-content fluorescence imaging to quantify the number of developing hepatic schizonts in primary rhesus hepatocytes infected with sporozoites from the M strain of P. cynomolgi [12] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum cytochrome b	ELQ-300		Pb Plasmodium berghei P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Pb is used in rodent model studies of malaria. ✖	-	9.0	pEC₅₀	12
Plasmodium falciparum cytochrome b	ELQ-300	pEC₅₀ 9.0 (EC₅₀ 1.02x10^-9 M) Luciferase bioluminescence assay to measure viability of exoerythrocytic forms [12] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum cytochrome b	compound 27 [PMID: 32945666]		Pb Plasmodium berghei P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Pb is used in rodent model studies of malaria. ✖	-	6.5	pIC₅₀	7
Plasmodium falciparum cytochrome b	compound 27 [PMID: 32945666]	pIC₅₀ 6.5 (IC₅₀ 3x10^-7 M) Luciferase bioluminescence assay to measure viability of exoerythrocytic forms (EEF) [7] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Plasmodium falciparum cyclin-dependent-like kinase CLK3	TCMDC-135051		Pb Plasmodium berghei P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Pb is used in rodent model studies of malaria. ✖	-	6.4	pEC₅₀	1
Plasmodium falciparum cyclin-dependent-like kinase CLK3	TCMDC-135051	pEC₅₀ 6.4 (EC₅₀ 4x10^-7 M) [1] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)
Unknown MOA	OSM-S-38		Pb Plasmodium berghei P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Pb is used in rodent model studies of malaria. ✖	-	7.7	pIC₅₀	18
Unknown MOA	OSM-S-38	pIC₅₀ 7.7 (IC₅₀ 1.9x10^-8 M) [18] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Unknown MOA	tafenoquine		Pc Plasmodium cynomolgi P. cynomolgi (Pc) is a malaria parasite that infects non-human primate species with the natural mammalian host being Asian Old World monkeys. Pc is used as a model for human P. vivax infection because these species are phylogenetically close and share a similar lifecycle, including the dormant liver form (hypnozoite). ✖	-	-	-	19
Unknown MOA	tafenoquine	P. cynomolgi infected primary rhesus hepatocyte assay, >90% inhibition of schizonts at 10µM [19] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Unknown MOA	ganaplacide		Py Plasmodium yoelii P. yoelii (Py) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Py is used in rodent model studies of malaria, in particular the immune response and in vaccine development. ✖	-	8.7	pIC₅₀	10
Unknown MOA	ganaplacide	pIC₅₀ 8.7 (IC₅₀ 2x10^-9 M) Sporozoite hepatocyte invasion assay [10] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Unknown MOA	primaquine		Pc Plasmodium cynomolgi P. cynomolgi (Pc) is a malaria parasite that infects non-human primate species with the natural mammalian host being Asian Old World monkeys. Pc is used as a model for human P. vivax infection because these species are phylogenetically close and share a similar lifecycle, including the dormant liver form (hypnozoite). ✖	-	6.4	pIC₅₀	19
Unknown MOA	primaquine	pIC₅₀ 6.4 (IC₅₀ 3.7x10^-7 M) P. cynomolgi infected primary rhesus hepatocyte assay, >90% inhibition of schizonts at 10µM [19] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Unknown MOA	NPC1161B		Pc Plasmodium cynomolgi P. cynomolgi (Pc) is a malaria parasite that infects non-human primate species with the natural mammalian host being Asian Old World monkeys. Pc is used as a model for human P. vivax infection because these species are phylogenetically close and share a similar lifecycle, including the dormant liver form (hypnozoite). ✖	-	-	-	19
Unknown MOA	NPC1161B	P. cynomolgi infected primary rhesus hepatocyte assay, >90% inhibition of schizonts at 10µM [19] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay
Unknown MOA	bulaquine		Pc Plasmodium cynomolgi P. cynomolgi (Pc) is a malaria parasite that infects non-human primate species with the natural mammalian host being Asian Old World monkeys. Pc is used as a model for human P. vivax infection because these species are phylogenetically close and share a similar lifecycle, including the dormant liver form (hypnozoite). ✖	-	-	-	19
Unknown MOA	bulaquine	P. cynomolgi infected primary rhesus hepatocyte assay, >90% inhibition of schizonts at 10µM [19] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Description: Parasite liver stage assay

References

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