Unraveling Coronin in Plasmodium falciparum: A Key Player in Artemisinin Resistance?

As resistance to artemisinin-based therapies continues to threaten malaria control efforts, researchers have turned their attention to a suite of genes in Plasmodium falciparum that may play a role in drug tolerance. Among them, coronin is emerging as an intriguing candidate worth watching.

What Is Coronin?

Coronin is a conserved actin-binding protein found in many eukaryotic organisms, including parasites like Plasmodium falciparum. It regulates the parasite’s actin cytoskeleton, impacting critical processes such as:

• Intracellular motility

• Vesicle trafficking

• Host-cell invasion

In P. falciparum, coronin helps maintain the structural integrity and dynamic remodeling of actin filaments—essential for the parasite’s survival and replication.

Coronin, Kelch13 and PI3K in Artemisinin Resistance?

Recent studies have observed mutations in the coronin gene (PF3D7_1251200) in laboratory-evolved artemisinin-resistant parasite lines, although such mutations are not yet widely seen in field isolates (Demas et al., 2018)

Possible Roles in Resistance:

• Altered actin dynamics may affect the stress response pathways under artemisinin exposure.

• Mutations in coronin may act synergistically with other resistance-associated genes, such as Kelch13.

How Does Coronin Compare to Kelch13 and PI3K?

Coronin is part of a larger molecular network possibly involved in resistance. Let’s briefly compare it with two other important players:

Kelch13 (K13): The Primary Genetic Marker

• Gene: PF3D7_1343700

• Role: K13 mutations (e.g., C580Y) are well-established markers for artemisinin resistance.

• Function: Involved in stress response and protein regulation, possibly through protein degradation pathways.

• Use in Surveillance: YES – routinely tracked globally (Mbengue et al., 2015).

PI3K (Phosphoinositide 3-Kinase): A Downstream Effector

• Gene: PF3D7_0515300

• Role: Not directly mutated in resistant parasites but becomes activated downstream of K13 mutations.

• Function: Catalyzes lipid signaling involved in vesicle trafficking and membrane dynamics.

• Connection: Increased PI3K activity and elevated PI3P levels are linked to K13-mediated resistance.

Comparison Table

Feature	Coronin	Kelch13	PI3K (PFPI3K)
Type of Protein	Actin-binding protein	Kelch-domain protein	Lipid kinase
Mutation Status	Observed in lab strains	Mutated in resistant strains	Not mutated (activity changes)
Role in Resistance	Emerging/unclear	Direct marker	Downstream effector
Use in Surveillance	No	Yes	No

Why It Matters

Understanding coronin's contribution to resistance may help refine our models of how artemisinin resistance evolves. Combined with confirmed markers like K13 and downstream players like PI3K, coronin could eventually:

• Serve as a supporting biomarker

• Highlight new targets for therapeutic intervention

• Reveal evolutionary pathways of drug resistance

Conclusion

While coronin is still under investigation, it underscores the complexity of antimalarial resistance and the need to look beyond single-gene models. With molecular tools like CRISPR-Cas9 gene editing, scientists are poised to uncover whether coronin mutations cause, enhance, or compensate for artemisinin resistance.

Bibliography

1. Demas, A. R., Sharma, A. I., Wong, W., Early, A. M., Redmond, S., Bopp, S., Neafsey, D. E., Volkman, S. K., Hartl, D. L., & Wirth, D. F. (2018). Mutations in Plasmodium falciparum actin-binding protein coronin confer reduced artemisinin susceptibility. PNAS, 115(50), 12799–12804.
   
   

2. Mbengue, A., Bhattacharjee, S., Pandharkar, T., Liu, H., Estiu, G., Stahelin, R. V., Rizk, S., Njimoh, D. L., Ryan, Y., Chotivanich, K., Nguon, C., Ghorbal, M., Lopez- Rubio, J.-J., Pfrender, M., Emrich, S., Mohandas, N., Dondorp, A. M., Wiest, O., & Haldar, K. (2015). A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria. Nature, 520(7549), 683–687. https://doi.org/10.1038/nature14412

3. Batugedara, G., Lu, X. M., Hristov, B., Abel, S., Chahine, Z., Hollin, T., Williams, D., Wang, T., Cort, A., Lenz, T., Thompson, T. A., & Prudhomme, J. (2023). Novel insights into the role of long non-coding RNA in the human malaria parasite, Plasmodium falciparum. Nature Communications, 14, 5086.

Why Malaria Medicines Sometimes Fail: A Guide to Plasmodium falciparum's Resistance Genes

Cracking the Code: Malaria Gene Mutations & Drug Resistance

Malaria is a disease caused by a parasite called Plasmodium falciparum, which is transmitted to humans through the bite of infected female Anopheles mosquitoes. In Ghana, the primary malaria vectors are Anopheles gambiae sensu stricto and Anopheles funestus, two species known for their efficiency in spreading malaria.

In Ghana and many parts of Africa, malaria is treated with a group of medicines called artemisinin-based combination therapies (ACTs). But sometimes, these treatments don’t work as well as they should. One major reason is that the parasite can develop resistance through changes in its genes—what scientists call mutations.

In this blog post, we’ll break down the important mutations that help the parasite survive even when drugs are used. We'll also explain how these changes work, what their names mean, and how malaria is currently treated.

Watch the video here:

What Are the Recommended Treatments for Malaria in Ghana?

The first choice treatment in Ghana for uncomplicated malaria is Artemisinin-based Combination Therapy (ACT). This means the medicine combines:

• An artemisinin derivative (which kills parasites fast),

• Plus a partner drug (which stays longer in the body to kill leftover parasites).

  
  

Common ACTs used in Ghana include:

• Artemether-Lumefantrine (AL)

• Artesunate-Amodiaquine (AS-AQ)

There’s also Sulfadoxine-Pyrimethamine (SP), which is used mainly for prevention during pregnancy (called IPTp).

Why Do We Use Partner Drugs with Artemisinin?

Artemisinin works very fast, clearing most parasites in about 48 hours, but it leaves the body quickly. Without a partner drug to clean up the rest, some parasites might survive and multiply again.

Partner drugs:

• Kill the remaining parasites after artemisinin finishes,

• Help prevent the parasite from becoming resistant to artemisinin,

• Lower the chance of the infection coming back (called recrudescence).

  
  

What Are Gene Mutations?

Mutations are small changes in the DNA of an organism. In malaria parasites, some mutations change the shape or behavior of proteins that drugs target. This means the drugs can no longer kill the parasite effectively.

Each mutation has a special code to describe it. For example:

K76T means:

• K: The normal amino acid is lysine.

• 76: The change happens at position 76 of the protein.

• T: The amino acid changes to threonine.

  
  

Important Genes and Mutations in Malaria Resistance

1. Chloroquine Resistance

• pfcrt gene: The key mutation is K76T.

• pfmdr1 gene: Other changes include N86Y, Y184F, and D1246Y.

• These mutations make it harder for chloroquine to kill the parasite.

2. Sulfadoxine-Pyrimethamine (SP) Resistance

• SP is a mix of two drugs that block folate synthesis in the parasite.

• pfdhfr gene: Mutations like N51I, C59R, and S108N make pyrimethamine less effective.

• pfdhps gene: Changes like A437G and K540E reduce the power of sulfadoxine.

When multiple mutations happen together (especially 3 in pfdhfr and 2 in pfdhps), the treatment may not work at all. This is called quintuple resistance.

3. Artemisinin Partial Resistance

• pfkelch13 gene: Changes like C580Y, R561H, and Y493H are signs that artemisinin might not clear the parasite quickly.

• These mutations don't stop artemisinin completely but slow down how fast the parasite is removed from the body.

  
  

What Are Haplotypes?

A haplotype is a group of mutations that are often found together in a parasite. For example:

CVIET is a haplotype found in chloroquine-resistant parasites. It shows changes at positions 72 to 76 in the pfcrt gene.

Codon	Wild Type	CVIET
72	C	C
73	V	V
74	M	I
75	N	E
76	K	T

The wild-type (non-mutated) version is called CVMNK. The mutant version CVIET includes the important K76T mutation.

Summary Table

Drug	Key Genes	Common Mutations	What Happens
Chloroquine	pfcrt, pfmdr1	K76T, N86Y	Drug no longer works
SP	pfdhfr, pfdhps	S108N, A437G	Partial or full treatment failure
Artemisinin	pfkelch13	C580Y, R561H	Parasite clears more slowly

Why This Matters

Knowing these mutations helps scientists and health workers:

• Monitor which drugs are still working

• Plan better treatments

• Prevent resistance from spreading

Conclusion

As a student learning about malaria, it’s important to understand not just how the disease is treated but also how the parasite can fight back. By studying gene mutations and resistance patterns, we can help protect future treatments and save lives.

If you want to learn more, explore topics like molecular epidemiology, PCR testing for resistance, and how these studies shape malaria policies in Ghana and beyond!

Bibliography

1. WHO. 2019. World malaria report 2019. https://www.who.int/publications -detail/world-malaria-report-2019. Accessed 9 December 2019.
   
   

2. WHO. 2009. Anti-malaria drug policy for Ghana, 2nd revised version 2009. http://apps.who.int/medicinedocs/en/d/Js18072en/.
   
   

3. Mensah, B. A., Aydemir, O., Myers-Hansen, J. L., Opoku, M., Hathaway, N. J., Marsh, P. W., Anto, F., Bailey, J., Abuaku, B., & Ghansah, A. (2020). Antimalarial Drug Resistance Profiling of Plasmodium falciparum Infections in Ghana Using Molecular Inversion Probes and Next-Generation Sequencing. Antimicrobial Agents and Chemotherapy, 64(4), e01423-19.

4. Mensah, B. A., Akyea-Bobi, N. E., & Ghansah, A. (2022). Genomic approaches for monitoring transmission dynamics of malaria: A case for malaria molecular surveillance in Sub–Saharan Africa. Frontiers in Epidemiology, 2, Article 939291. https://doi.org/10.3389/fepid.2022.939291
   
   

5. Verity, R., Aydemir, O., Brazeau, N. F., et al. (2020). The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC. Nature Communications, 11, Article 2107. https://doi.org/10.1038/s41467-020-15779-8
   
   

6. Wei, X., Brashear, A., Siddiqui, F., Agyekum, G., Lucky, A., Chim-Ong, A., Afrane, Y., Miao, J., Wang, C., Amoah, L., & Cui, L. (2025). Plasmodium falciparum genetic diversity and multiplicity of infection in northern and southern Ghana assessed by amplicon sequencing. Infection, Genetics and Evolution, 131, 105754.
   
   

7. Ghansah, A., Tiedje, K. E., Argyropoulos, D. C., Onwona, C. O., Deed, S. L., Labbé, F., Oduro, A. R., Koram, K. A., Pascual, M., & Day, K. P. (2023). Comparison of molecular surveillance methods to assess changes in the population genetics of Plasmodium falciparum in high transmission. Frontiers in Parasitology, 2, Article 1067966. https://doi.org/10.3389/fpara.2023.1067966