Bioinformatics On the Quest for New Antileishmanial Drugs

A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366).

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 5583

Special Issue Editor


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Guest Editor
Vicerrectorado de Investigación, Universidad Católica de Santa María, Urb. San José s/n—Umacollo, Arequipa 04000, Peru
Interests: Leishmaniasis; molecular parasitology; drug discovery; molecular pharmacology

Special Issue Information

Dear Colleagues,

Leishmaniasis is caused by parasites of the genus Leishmania (Kinetoplastida, Trypanosomatidae), where roughly 20 parasite species can infect mammals and many of them can lead to human disease. Around 380 million people are at risk for leishmaniasis in 98 countries, and from 1.5 to 2.0 million cases are reported each year, with a significant morbidity and fatality rate. For human use, no vaccine is yet available, and current chemotherapy has several harmful side effects. It is still difficult to transform new research into cost-efficient and accessible biotechnology solutions that attempt to manage and/or enhance the conditions of the disease's therapy. Although new approaches and advancements in antileishmanial drug research are needed for new therapeutic candidates, the biggest obstacles to this goal's success depend on worldwide contributions. Drug discovery and development now heavily rely on bioinformatic methods, which can also lead to quicker, safer, and less expensive drug advancement. Both the pharmaceutical industry and academia rely on in silico drug discovery and development, which has been also focused on new therapeutics against leishmaniasis. While encouraging studies that are followed by in vitro and/or in vivo validation, we invite authors to submit original research articles presenting bioinformatic analysis applied to develop potential novel therapeutics against leishmaniasis.

Potential topics include but are not limited to:

  • Nanotechnology-based formulation;
  • Molecular docking and molecular dynamics simulations;
  • Omics data for new target selection;
  • Virtual screening.

Dr. Miguel Angel Chávez-Fumagalli
Guest Editor

Manuscript Submission Information

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Keywords

  • bioinformatics
  • drug targets
  • drug discovery
  • virtual screening
  • molecular docking
  • pharmacogenomics
  • pharmacogenetics

Published Papers (2 papers)

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Research

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17 pages, 8931 KiB  
Article
Targeting with Structural Analogs of Natural Products the Purine Salvage Pathway in Leishmania (Leishmania) infantum by Computer-Aided Drug-Design Approaches
by Haruna Luz Barazorda-Ccahuana, Eymi Gladys Cárcamo-Rodriguez, Angela Emperatriz Centeno-Lopez, Alexsandro Sobreira Galdino, Ricardo Andrez Machado-de-Ávila, Rodolfo Cordeiro Giunchetti, Eduardo Antonio Ferraz Coelho and Miguel Angel Chávez-Fumagalli
Trop. Med. Infect. Dis. 2024, 9(2), 41; https://doi.org/10.3390/tropicalmed9020041 - 3 Feb 2024
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Abstract
Visceral Leishmaniasis (VL) has a high death rate, with 500,000 new cases and 50,000 deaths occurring annually. Despite the development of novel strategies and technologies, there is no adequate treatment for the disease. Therefore, the purpose of this study is to find structural [...] Read more.
Visceral Leishmaniasis (VL) has a high death rate, with 500,000 new cases and 50,000 deaths occurring annually. Despite the development of novel strategies and technologies, there is no adequate treatment for the disease. Therefore, the purpose of this study is to find structural analogs of natural products as potential novel drugs to treat VL. We selected structural analogs from natural products that have shown antileishmanial activities, and that may impede the purine salvage pathway using computer-aided drug-design (CADD) approaches. For these, we started with the vastly studied target in the pathway, the adenine phosphoribosyl transferase (APRT) protein, which alone is non-essential for the survival of the parasite. Keeping this in mind, we search for a substance that can bind to multiple targets throughout the pathway. Computational techniques were used to study the purine salvage pathway from Leishmania infantum, and molecular dynamic simulations were used to gather information on the interactions between ligands and proteins. Because of its low homology to human proteins and its essential role in the purine salvage pathway proteins network interaction, the findings further highlight the significance of adenylosuccinate lyase protein (ADL) as a therapeutic target. An analog of the alkaloid Skimmianine, N,N-diethyl-4-methoxy-1-benzofuran-6-carboxamide, demonstrated a good binding affinity to APRT and ADL targets, no expected toxicity, and potential for oral route administration. This study indicates that the compound may have antileishmanial activity, which was granted in vitro and in vivo experiments to settle this finding in the future. Full article
(This article belongs to the Special Issue Bioinformatics On the Quest for New Antileishmanial Drugs)
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Review

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13 pages, 321 KiB  
Review
Molecular Docking and Molecular Dynamics Simulations in Related to Leishmania donovani: An Update and Literature Review
by Mabel R. Challapa-Mamani, Eduardo Tomás-Alvarado, Angela Espinoza-Baigorria, Darwin A. León-Figueroa, Ranjit Sah, Alfonso J. Rodriguez-Morales and Joshuan J. Barboza
Trop. Med. Infect. Dis. 2023, 8(10), 457; https://doi.org/10.3390/tropicalmed8100457 - 26 Sep 2023
Cited by 5 | Viewed by 3462
Abstract
Leishmaniasis, a disease caused by Leishmania parasites and transmitted via sandflies, presents in two main forms: cutaneous and visceral, the latter being more severe. With 0.7 to 1 million new cases each year, primarily in Brazil, diagnosing remains challenging due to diverse disease [...] Read more.
Leishmaniasis, a disease caused by Leishmania parasites and transmitted via sandflies, presents in two main forms: cutaneous and visceral, the latter being more severe. With 0.7 to 1 million new cases each year, primarily in Brazil, diagnosing remains challenging due to diverse disease manifestations. Traditionally, the identification of Leishmania species is inferred from clinical and epidemiological data. Advances in disease management depend on technological progress and the improvement of parasite identification programs. Current treatments, despite the high incidence, show limited efficacy due to factors like cost, toxicity, and lengthy regimens causing poor adherence and resistance development. Diagnostic techniques have improved but a significant gap remains between scientific progress and application in endemic areas. Complete genomic sequence knowledge of Leishmania allows for the identification of therapeutic targets. With the aid of computational tools, testing, searching, and detecting affinity in molecular docking are optimized, and strategies that assess advantages among different options are developed. The review focuses on the use of molecular docking and molecular dynamics (MD) simulation for drug development. It also discusses the limitations and advancements of current treatments, emphasizing the importance of new techniques in improving disease management. Full article
(This article belongs to the Special Issue Bioinformatics On the Quest for New Antileishmanial Drugs)
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