Natural Inhibitors for Enzymes Linked to Disease Spread in Humans

Jenn Hoskins
8th July, 2024

Natural Inhibitors for Enzymes Linked to Disease Spread in Humans

Image Source: Natural Science News, 2024

Key Findings

  • The study by the Pasteur Institute of Iran focused on Anopheles mosquitoes and the role of Carboxypeptidase B (CPB) in Plasmodium parasite development
  • Researchers found that natural inhibitors from tomato and potato (CPiSt) could effectively inhibit CPB enzymes in mosquitoes
  • The study suggests that CPiSt and its mutant form are stable and promising candidates for disrupting malaria transmission
Malaria remains one of the most significant parasitic diseases globally, causing millions of infections and up to a million deaths annually[2][3]. Despite advancements in sanitary conditions and antimalarial drugs, the disease persists, particularly in underdeveloped regions. The emergence of drug-resistant malaria parasites has further complicated control efforts, necessitating new strategies to combat the disease[2]. One promising approach involves targeting the mosquito phase of the Plasmodium parasite's life cycle, particularly by inhibiting enzymes essential for the parasite's development within the mosquito[2]. Recent research conducted by the Pasteur Institute of Iran has focused on the role of Carboxypeptidase B (CPB) in Anopheles mosquitoes, which is crucial for breaking down blood and releasing amino acids that promote Plasmodium sexual development in the mosquito midgut[1]. The study aimed to assess the inhibitory effectiveness of carboxypeptidase inhibitors derived from tomato, potato (CPiSt), and leech against two specific enzymes, CPBAs1 and CPBAs2, in Anopheles stephensi mosquitoes. To achieve this, the researchers used computational methods to predict the tertiary structures of CPB inhibitors and examined their interaction with CPBAs1 and CPBAs2 through molecular docking. Molecular docking is a technique that predicts the preferred orientation of one molecule to a second when bound to each other, which helps in understanding the binding affinity and activity of the inhibitors. The study compared the effectiveness of these natural inhibitors with four licensed medications known to reduce CPB activity in mosquitoes. The findings revealed that both CPiSt and its mutant form showed promise as potential candidates for further evaluation in malaria control strategies. The inhibitors demonstrated similar binding affinities to the active sites of CPBAs1 and CPBAs2, comparable to those of the licensed drugs. This suggests that CPiSt and its mutant form could effectively inhibit the CPB enzymes, thereby disrupting the Plasmodium parasite's development within the mosquito. The study's use of molecular dynamics simulations further evaluated the stability of the complexes containing CPiSt and its mutant form. Molecular dynamics simulations are computational methods that model the physical movements of atoms and molecules over time, providing insights into the stability and behavior of molecular complexes. The results indicated that the complexes were stable, reinforcing the potential of CPiSt and its mutant form as viable inhibitors for CPB enzymes in Anopheles mosquitoes. This research builds on previous findings that have identified various targets within the mosquito phase of the Plasmodium life cycle as potential intervention points. For instance, earlier studies have highlighted the importance of targeting the mosquito midgut, where Plasmodium undergoes several transformation processes, offering numerous potential blocking targets[2]. Additionally, the characterization of genes like cpbAg1, which codes for a zinc-carboxypeptidase in Anopheles gambiae, has provided insights into the digestive enzymes involved in Plasmodium development within mosquitoes[4]. By focusing on CPB inhibitors derived from natural sources such as tomato and potato, the study offers a novel approach to malaria control that could complement existing strategies. The potential use of these inhibitors in paratransgenesis—a technique where genetically modified symbiotic bacteria are introduced into mosquito populations to disrupt Plasmodium development—could provide a sustainable and environmentally friendly method to reduce malaria transmission. In conclusion, the research conducted by the Pasteur Institute of Iran represents a significant step forward in the quest to develop new malaria control methods. By targeting the CPB enzymes in Anopheles mosquitoes, the study offers a promising approach to disrupt the Plasmodium life cycle and reduce malaria transmission. These findings, combined with previous research on mosquito midgut enzymes and transmission-blocking strategies, highlight the potential of innovative, multi-faceted approaches to combat this persistent global health challenge[2][4].

MedicineBiochemAnimal Science

References

Main Study

1) Leech, potato, and tomato carboxypeptidase inhibitors against Anopheles stephensi carboxypeptidase B1 and B2.

Published 5th July, 2024

https://doi.org/10.1016/j.abb.2024.110086


Related Studies

2) Transmission-Blocking Strategies Against Malaria Parasites During Their Mosquito Stages.

https://doi.org/10.3389/fcimb.2022.820650


3) Blood-stage malaria vaccines - recent progress and future challenges.

https://doi.org/10.1179/136485910X12647085215534


4) cpbAg1 encodes an active carboxypeptidase B expressed in the midgut of Anopheles gambiae.

Journal: Insect molecular biology, Issue: Vol 14, Issue 2, Apr 2005



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