Plasmodium SEY1 is a novel druggable target that contributes to imidazolopiperazine mechanism of action DOI
Elizabeth A. Winzeler, Krypton Carolino, Mariana Laureano de Souza

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

Abstract The precise mode of action ganaplacide (KAF156), a phase III antimalarial candidate, remains elusive. Here we employ omics-based methods with the closely related chemical analog, GNF179, to search for potential Plasmodium targets. Ranking targets derived from genetics and proteomic affinity chromatography methodologies identifies SEY1, or Synthetic Enhancement YOP1, which is predicted encode an essential dynamin-like GTPase implicated in homotypic fusion endoplasmic reticulum (ER) membranes. We demonstrate that GNF179 decreases SEY1 melting temperature. further show binds recombinant subsequently inhibits its activity, required maintaining ER architecture. Using ultrastructure expansion microscopy, find treatment changes parasite Golgi morphology. also confirm SEY1 gene P. falciparum. These data suggest may contribute mechanism imidazolopiperazines new attractive druggable target.

Language: Английский

Recent perspectives in clinical development of malaria vaccines DOI Creative Commons
Jack Feehan, Magdalena Plebanski, Vasso Apostolopoulos

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 15, 2025

Citations

0
Challenges and Strategies in Administering Anesthesia to Pregnant Patients With Malaria: A Comprehensive Review DOI Open Access

Renuka Patond,

Nikhil Bhalerao

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 20, 2024

Malaria remains a significant global health challenge, particularly in sub-Saharan Africa, where its impact on pregnant women and their fetuses is profound. The disease's complex interaction with pregnancy introduces unique challenges anesthesia management, necessitating thorough understanding of both malaria implications for anesthetic care. This review aims to explore the multifaceted issues associated patients malaria, examining disease specific considerations required effective management. A comprehensive current literature was conducted, focusing physiological effects pregnancy, complications, related challenges. synthesizes findings from clinical studies, case reports, expert guidelines provide an overview best practices strategies. can lead severe complications such as maternal anemia, placental insufficiency, preterm labor, all which complicate identifies key anesthesia, including choice techniques, drug interactions, fluid Specific include managing ensuring adequate hemodynamic stability, mitigating potential risks medications. Effective management requires nuanced approach that addresses changes pregnancy. underscores need tailored strategies highlights areas further research enhance patient safety outcomes. Recommendations are provided guide clinicians optimizing care this vulnerable population.

Language: Английский

Citations

0
Plasmodium SEY1 is a novel druggable target that contributes to imidazolopiperazine mechanism of action DOI
Elizabeth A. Winzeler, Krypton Carolino, Mariana Laureano de Souza

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

Abstract The precise mode of action ganaplacide (KAF156), a phase III antimalarial candidate, remains elusive. Here we employ omics-based methods with the closely related chemical analog, GNF179, to search for potential Plasmodium targets. Ranking targets derived from genetics and proteomic affinity chromatography methodologies identifies SEY1, or Synthetic Enhancement YOP1, which is predicted encode an essential dynamin-like GTPase implicated in homotypic fusion endoplasmic reticulum (ER) membranes. We demonstrate that GNF179 decreases SEY1 melting temperature. further show binds recombinant subsequently inhibits its activity, required maintaining ER architecture. Using ultrastructure expansion microscopy, find treatment changes parasite Golgi morphology. also confirm SEY1 gene P. falciparum. These data suggest may contribute mechanism imidazolopiperazines new attractive druggable target.

Language: Английский

Citations

0