Mechanism of praziquantel action at a parasitic flatworm ion channel.

ABSTRACT: Praziquantel (PZQ) is an essential medicine for treating parasitic flatworm infections such as schistosomiasis, which afflicts over 250 million people. However, PZQ is not universally effective, lacking activity against liver flukes of the Fasciola genus. The reason for this insensitivity is unclear, as the mechanism of PZQ action is unknown. Here, we use ligand- and target-based methods to demonstrate that PZQ activates a transient receptor potential melastatin ion channel (TRPM_PZQ) in schistosomes by engaging a hydrophobic ligand binding pocket within the voltage sensor–like domain of the channel to cause calcium entry and worm paralysis. PZQ activates TRPM_PZQ homologs in other PZQ-sensitive flukes, but not Fasciola hepatica. However, a single amino ac

SUBMITTER: Park SK 

PROVIDER: S-EPMC8855674 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature