An experimental target-based platform in yeast for screening Plasmodium vivax deoxyhypusine synthase inhibitors.

The enzyme deoxyhypusine synthase (DHS) catalyzes the first step in the post-translational modification of the eukaryotic translation factor 5A (eIF5A). This is the only protein known to contain the amino acid hypusine, which results from this modification. Both eIF5A and DHS are essential for cell viability in eukaryotes, and inhibiting DHS is a promising strategy to develop new therapeutic alternatives.

A novel 4-aminoquinoline chemotype with multistage antimalarial activity and lack of cross-resistance with PfCRT and PfMDR1 mutants.

Artemisinin-based combination therapy (ACT) is the mainstay of effective treatment of Plasmodium falciparum malaria. However, the long-term utility of ACTs is imperiled by widespread partial artemisinin resistance in Southeast Asia and its recent emergence in parts of East Africa. This underscores the need to identify chemotypes with new modes of action (MoAs) to circumvent resistance to ACTs.

Innovative Multistage ML-QSAR Models for Malaria: From Data to Discovery.

Malaria presents a significant challenge to global public health, with around 247 million cases estimated to occur annually worldwide. The growing resistance of parasites to existing therapies underscores the urgent need for new and innovative antimalarial drugs. This study leveraged artificial intelligence (AI) to tackle this complex challenge.

Unveiling the Antiviral Capabilities of Targeting Human Dihydroorotate Dehydrogenase against SARS-CoV-2.

The urgent need for effective treatments against emerging viral diseases, driven by drug-resistant strains and new viral variants, remains critical. We focus on inhibiting the human dihydroorotate dehydrogenase (DHODH), one of the main enzymes responsible for pyrimidine nucleotide synthesis. This strategy could impede viral replication without provoking resistance.

Selective Bias Virtual Screening for Discovery of Promising Antimalarial Candidates targeting Plasmodium N-Myristoyltransferase.

Malaria remains a significant public health challenge, with being the species responsible for the most prevalent form of the disease. Given the limited therapeutic options available, the search for new antimalarials against is urgent. This study aims to identify new inhibitors for -myristoyltransferase (PvNMT), an essential drug target against malaria.

The activity of methylene blue against asexual and sexual stages of .

Methylene blue (MB) is an alternative for combating drug-resistant malaria parasites. Its transmission-blocking potential has been demonstrated in murine models, , and in clinical trials. MB shows high efficacy against asexual stages; however, its efficacy in sexual stages is unknown.

Rosette formation by gametocytes favors the infection in .

a public health problem and the most common type of malaria outside sub-Saharan Africa. The capacity of cytoadhesion, rosetting, and liver latent phase development could impact treatment and disease control. Although the ability to gametocyte develop rosetting is known, it is not yet clear which role it plays during the infection and transmission process to the mosquito.

Crotofolane Diterpenoids and Other Constituents Isolated from .

Six new crotofolane diterpenoids (-) and 13 known compounds (-) were isolated from the MeOH-CHCl (1:1, v/v) extracts of the leaves and stem bark of . The structures of the new compounds were elucidated by extensive analysis of spectroscopic and mass spectrometric data. The structure of crotokilwaepoxide A () was confirmed by single-crystal X-ray diffraction, allowing for the determination of its absolute configuration.

Gametocytes Adherence to Bone Marrow Endothelial Cells.

In a infection, it was shown a proportionally increased on gametocyte distribution within the bone marrow aspirant, suggesting a role of this organ as a reservoir for this parasite stage. Here, we evaluated the cytoadhesive capacity of gametocytes to bone marrow endothelial cells (HBMEC) and investigated the involvement of some receptors in the cytoadhesion process by using transfected CHO cells (CHO-ICAM1, CHO-CD36 and CHO-VCAM), wild type (CHO-K1) or deficient in heparan and chondroitin sulfate (CHO-745). cytoadhesion assays were performed using a total of 44  isolates enriched in gametocyte stages by Percoll gradient in the different cell lines.

Violacein-Induced Chaperone System Collapse Underlies Multistage Antiplasmodial Activity.

Antimalarial drugs with novel modes of action and wide therapeutic potential are needed to pave the way for malaria eradication. Violacein is a natural compound known for its biological activity against cancer cells and several pathogens, including the malaria parasite, (Pf). Herein, using chemical genomic profiling (CGP), we found that violacein affects protein homeostasis.

The role of the peritrophic matrix and red blood cell concentration in Plasmodium vivax infection of Anopheles aquasalis.

Background: Plasmodium vivax is predominant in the Amazon region, and enhanced knowledge of its development inside a natural vector, Anopheles aquasalis, is critical for future strategies aimed at blocking parasite development. The peritrophic matrix (PM), a chitinous layer produced by the mosquito midgut in response to blood ingestion, is a protective barrier against pathogens. Plasmodium can only complete its life-cycle, and consequently be transmitted to a new host, after successfully passing this barrier.