In Silico Analysis of Potential Drug Targets for Protozoan Infections

Juárez-Saldívar, Alfredo; Campillo, Nuria E.; Ortiz-Pérez, Eyrá; Paz-González, Alma D.; Saavedra, Emma; Rivera, Gildardo

doi:10.2174/1573406418666220816121912

Cited by 2 publications

(1 citation statement)

References 47 publications

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“…However, by enabling the quicker discovery of therapeutic targets, computational tools lead to an advancement in the drug development process [40]. The initial stage of creating medications involves the identification of promising targets, within Plasmodium falciparum (a type of protozoan) Essential proteins are thought to be the best targets for antimalarial treatment because there is the maximum chances that most drugs will interact with them [41]. Recent research found that Plasmodium falciparum has a total of 5,389 proteins.…”

Section: Discussionmentioning

confidence: 99%

Exploring Harmala Alkaloids as Novel Antimalarial Agents againstPlasmodium falciparumthrough Bioinformatics Approaches

Dipto,

Shariar,

Saha

et al. 2024

Preprint

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Malaria, caused by thePlasmodium falciparum, remains a significant global health challenge, with Plasmodium falciparum accounting for approximately 50% of cases and posing a considerable threat. Despite advances in control measures, malaria continues to cause an estimated one million deaths annually. The complex lifecycle ofP. falciparum, involving both vertebrate hosts and Anopheles mosquitoes, complicates eradication efforts. The parasite’s resistance to existing antimalarial drugs, along with medication toxicity, necessitates innovative therapeutic approaches.Recent research has revealed that harmine, an alkaloid produced by an endophytic gut bacterium of Anopheles mosquitoes, can impede the transmission of the malarial parasite to humans by inhibiting a crucial life stage. This study investigates harmala alkaloids, sourced from plants and bacteria such asPeganum harmala, as potential alternatives to conventional antimalarial drugs. Notably, harmine and harmaline have shown promising antimalarial activity by inhibiting the essential enzyme protein kinase 4 (PK4), which is vital for the parasite’s survival. These compounds exhibit lower toxicity, effectively inhibiting both the blood stage growth and transmission of the parasite. Using in silico methodologies, including ADME analysis, molecular docking, MD simulation, and toxicity analysis, this study identifies harmala alkaloids as potential inhibitors against crucialP. falciparumproteins. Targeting proteins essential for the parasite’s survival, similar to established drugs like pfCRT protein, lays the foundation for developing effective antimalarial treatments. The comprehensive screening of harmala alkaloid molecules opens avenues for the pharmaceutical industry to tackle challenges related to drug resistance and toxicity, offering a promising route for the biorational management of malaria.

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Section: Discussionmentioning

confidence: 99%

Exploring Harmala Alkaloids as Novel Antimalarial Agents againstPlasmodium falciparumthrough Bioinformatics Approaches

Dipto,

Shariar,

Saha

et al. 2024

Preprint

View full text Add to dashboard Cite

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Pathogenicity and virulence of Entamoeba histolytica , the agent of amoebiasis

Guillén

2023

Virulence

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The amoeba parasite Entamoeba histolytica is the causative agent of human amebiasis, an enteropathic disease affecting millions of people worldwide. This ancient protozoan is an elementary example of how parasites evolve with humans, e.g. taking advantage of multiple mechanisms to evade immune responses, interacting with microbiota for nutritional and protective needs, utilizing host resources for growth, division, and encystation. These skills of E. histolytica perpetuate the species and incidence of infection. However, in 10% of infected cases, the parasite turns into a pathogen; the host-parasite equilibrium is then disorganized, and the simple lifecycle based on two cell forms, trophozoites and cysts, becomes unbalanced. Trophozoites acquire a virulent phenotype which, when non-controlled, leads to intestinal invasion with the onset of amoebiasis symptoms. Virulent E. histolytica must cross mucus, epithelium, connective tissue and possibly blood. This highly mobile parasite faces various stresses and a powerful host immune response, with oxidative stress being a challenge for its survival. New emerging research avenues and omics technologies target gene regulation to determine human or parasitic factors activated upon infection, their role in virulence activation, and in pathogenesis; this research bears in mind that E. histolytica is a resident of the complex intestinal ecosystem. The goal is to eradicate amoebiasis from the planet, but the parasitic life of E. histolytica is ancient and complex and will likely continue to evolve with humans. Advances in these topics are summarized here.

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In Silico Analysis of Potential Drug Targets for Protozoan Infections

Cited by 2 publications

References 47 publications

Exploring Harmala Alkaloids as Novel Antimalarial Agents againstPlasmodium falciparumthrough Bioinformatics Approaches

Exploring Harmala Alkaloids as Novel Antimalarial Agents againstPlasmodium falciparumthrough Bioinformatics Approaches

Pathogenicity and virulence of Entamoeba histolytica , the agent of amoebiasis

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