Healthy sweet inhibitor of Plasmodium falciparum aquaglyceroporin

TL;DR

This study identifies erythritol as a safe, effective inhibitor of Plasmodium falciparum aquaglyceroporin, potentially leading to a new malaria treatment by blocking parasite nutrient transport.

Contribution

The paper demonstrates through extensive in silico simulations that erythritol can strongly inhibit PfAQP, a key protein in malaria parasites, revealing a novel drug candidate.

Findings

Erythritol inhibits PfAQP's transport of multiple permeants.

IC50 of erythritol is in the high nanomolar range.

Erythritol is a safe, sweetener with potential as an antimalarial drug.

Abstract

Plasmodium falciparum aquaglyceroporin (PfAQP) is a multifunctional channel protein in the plasma membrane of the malarial parasite that causes the most severe form of malaria infecting more than a million people a year. Finding a novel way to inhibit PfAQP, I conducted 3+ microseconds in silico experiments of an atomistic model of the PfAQP-membrane system and computed the chemical-potential profiles of six permeants (erythritol, water, glycerol, urea, ammonia, and ammonium) that can be efficiently transported across P. falciparum's plasma membrane through PfAQP's conducting pore. The profiles show that, with all the existent in vitro data being supportive, erythritol, a permeant of PfAQP itself having a deep ditch in its permeation passageway, strongly inhibits PfAQP's functions of transporting water, glycerol, urea, ammonia, and ammonium (The IC50 is in the range of high nanomolars). This suggests the possibility that erythritol, a sweetener generally considered safe, may be the drug needed to kill the malarial parasite in vivo without causing serious side effects.