Human Parasitic Diseases: Challenges and Progress in Drug Discovery and Target Identification

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Parasitic Pathogens".

Deadline for manuscript submissions: 28 February 2025 | Viewed by 1714

Special Issue Editors


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Guest Editor
Center for Neurosciences and Cell Biology, University of Coimbra, 3060-197 Cantanhede, Portugal
Interests: drug discovery; high content screening; Salmonella; parasitology; Trypanosoma cruzi

E-Mail Website
Guest Editor
Center for Neurosciences and Cell Biology, University of Coimbra, 3060-197 Cantanhede, Portugal
Interests: antimicrobials; bacteriology; parasitology; drugs and functional screening

E-Mail Website
Guest Editor
Laboratory of Cellular Ultrastructure Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Interests: parasitic diseases; functional genomics; target identification; Trypanosoma cruzi; high resolution microscopy

Special Issue Information

Dear Colleagues, 

Protozoa, helminths, and ectoparasites are the main causative agents of human parasitic diseases, which generate a significant global health burden and are strongly related to poverty, low healthcare assistance, and poor sanitary and housing conditions. Because they affect the most vulnerable communities in low-income regions of the world, parasitic diseases have been historically neglected by the pharmaceutical industry and by market-guided drug-discovery campaigns. Consequently, few safe and effective antiparasitic treatments have been developed in recent years, despite the enormous efforts from academia and non-governmental initiatives. Current treatments for most human parasitic diseases rely on old and nonspecific drugs, frequently associated with variable efficacy and poor selectivity. Additionally, in comparison to other human pathogenesis, significantly less is known about relevant molecular players and essential pathways involved in host–parasite interactions, hampering target-based drug-discovery approaches in this area. There is a need for an in-depth understanding of specific host–parasite interplays, aligned with the uncovering of novel relevant targets to favor the discovery and development of new, efficacious, and safe drugs for human parasitic diseases. 

This Special Issue is focused on the recent progress and challenges of target identification and drug discovery for human parasitic diseases. We invite you to submit original and review articles related to innovative approaches on early drug discovery, host–pathogen interactions, and target identification for human diseases caused by protozoa, helminths and ectoparasites. 

Dr. Caio Haddad Franco
Dr. Laura Maria Alcântara
Dr. Normanda Souza Melo
Guest Editors

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Keywords

  • human parasitic diseases
  • drug discovery and development
  • target identification
  • host–pathogen interactions
  • mechanism of action

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Published Papers (1 paper)

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Research

16 pages, 1937 KiB  
Article
Peptide-Alkoxyamine Drugs: An Innovative Approach to Fight Schistosomiasis: “Digging Their Graves with Their Forks”
by Ange W. Embo-Ibouanga, Michel Nguyen, Jean-Patrick Joly, Mathilde Coustets, Jean-Michel Augereau, Lucie Paloque, Nicolas Vanthuyne, Raphaël Bikanga, Anne Robert, Françoise Benoit-Vical, Gérard Audran, Philippe Mellet, Jérôme Boissier and Sylvain R. A. Marque
Pathogens 2024, 13(6), 482; https://doi.org/10.3390/pathogens13060482 - 6 Jun 2024
Cited by 2 | Viewed by 1094
Abstract
The expansion of drug resistant parasites sheds a serious concern on several neglected parasitic diseases. Our recent results on cancer led us to envision the use of peptide-alkoxyamines as a highly selective and efficient new drug against schistosome adult worms, the etiological agents [...] Read more.
The expansion of drug resistant parasites sheds a serious concern on several neglected parasitic diseases. Our recent results on cancer led us to envision the use of peptide-alkoxyamines as a highly selective and efficient new drug against schistosome adult worms, the etiological agents of schistosomiasis. Indeed, the peptide tag of the hybrid compounds can be hydrolyzed by worm’s digestive enzymes to afford a highly labile alkoxyamine which homolyzes spontaneously and instantaneously into radicals—which are then used as a drug against Schistosome adult parasites. This approach is nicely summarized as digging their graves with their forks. Several hybrid peptide-alkoxyamines were prepared and clearly showed an activity: two of the tested compounds kill 50% of the parasites in two hours at a concentration of 100 µg/mL. Importantly, the peptide and alkoxyamine fragments that are unable to generate alkyl radicals display no activity. This strong evidence validates the proposed mechanism: a specific activation of the prodrugs by the parasite proteases leading to parasite death through in situ alkyl radical generation. Full article
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