Malaria Egress Pathway and UA2239 Inhibition

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Questions and Answers

What is the ED50 of UA2239 in inhibiting berghei-infected mice?

0.1 mg/kg

0.5 mg/kg (correct)

1.0 mg/kg

2.0 mg/kg

What does a high selectivity index (SI > 10,000) for UA2239 indicate?

Broad-spectrum antiviral properties

Low toxicity to mammalian cells (correct)

High activity on mammalian cells

Enhanced side effects

Which pathway is involved in the egress of merozoites from red blood cells?

cGMP-PDE pathway

Calcium-dependent pathway

cGMP-PKG dependent pathway (correct)

cAMP-PKA pathway

What is the expected effect of inhibiting PfPDE?

Induced egress of immature merozoites Signup and view all the answers

Which chemical class does Compound 2 (C2) belong to?

Imidazopyridines Signup and view all the answers

How does UA2239 affect different stages of the parasite life cycle?

Inhibits both intraerythrocytic cycle and gametogenesis Signup and view all the answers

The primary mechanism of action for nucleoside and nucleotide analogues involves what process?

Conversion into poly-phosphorylated derivatives Signup and view all the answers

What is the result of inhibiting PfPKG in malaria parasites?

Impairment of merozoite egress from red blood cells Signup and view all the answers

What is the target of the compound UA2239 in the malaria parasite?

Guanylate cyclase (PfGCα) Signup and view all the answers

What distinguishes UA2239's mechanism of action from traditional antimalarial therapies?

It impairs cyclic-GMP synthesis. Signup and view all the answers

In which aspect has UA2239 shown significant promise?

Inhibiting the growth of Plasmodium in vitro and in animal models. Signup and view all the answers

What does UA2239 inhibit in the malaria lifecycle?

Egress of merozoites and gametes from erythrocytes. Signup and view all the answers

What phenomenon was observed with UA2239-resistant P.falciparum lines?

Mutations in cGMP-dependent protein kinase (PKG). Signup and view all the answers

How many deaths due to malaria were estimated in 2022?

608,000 Signup and view all the answers

What role does guanylate cyclase (PfGCα) play in the context of UA2239's action?

It is inhibited by UA2239. Signup and view all the answers

What is the main urgent need mentioned for antimalarial therapies?

To combat the spread of malaria parasite resistance. Signup and view all the answers

What remains a critical method in the fight against malaria despite the development of vaccines?

Chemotherapy Signup and view all the answers

Which of the following accurately describes the life cycle of the malaria parasite in humans?

They initially multiply in liver cells before entering the bloodstream. Signup and view all the answers

What is a significant issue faced in malaria treatment currently?

Emergence of artemisinin-resistant strains Signup and view all the answers

What is the expected focus of future antimalarial treatments?

Targeting multiple stages of the parasite's life cycle Signup and view all the answers

Which of the following statements describes the activity of the compound UA2239?

It inhibits parasite growth effectively in vitro. Signup and view all the answers

What does the IC50 value indicate in the context of UA2239's effectiveness?

The concentration required to inhibit 50% of parasite growth. Signup and view all the answers

What is the role of gametocytes in the malaria parasite's life cycle?

To mate in the mosquito gut after a blood meal. Signup and view all the answers

What has recently been synthesized as a novel antimalarial treatment?

Acyclo-nucleoside phosphonates (ANPs) Signup and view all the answers

Study Notes

Malaria cGMP-PKG Dependent Egress Pathway Inhibited by UA2239

A potent acyclic nucleoside phosphonate, UA2239, inhibits the malaria cGMP-PKG dependent egress pathway.
UA2239 inhibits Plasmodium growth in vitro and in animal models.
It blocks the egress of merozoites and gametes from erythrocytes.
UA2239 resistance in P. falciparum is linked to mutations in cGMP-dependent protein kinase (PKG).
However, UA2239 doesn't directly target PKG; instead, it lowers cGMP levels.
This, in turn, inhibits the parasite's guanylate cyclase (PfGCa), which is a crucial component of the cGMP-dependent egress pathway.
UA2239 impairs cyclic-GMP synthesis.
This uniquely targets the unique mechanism of action by targeting cyclic GMP synthesis.

Abbreviations

C2: compound 2
CQ: chloroquine
DHA: dihydroartemisinin
GC: guanylate cyclase
GER parasites: genome-edited resistant parasites

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Description

This quiz explores the role of UA2239 in inhibiting the malaria cGMP-PKG dependent egress pathway. Test your understanding of its effects on Plasmodium growth, mutation links, and its unique mechanism of action targeting cyclic GMP synthesis.