  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.
