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A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609.


ABSTRACT: Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite-infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite's sodium efflux pump (adenosine triphosphate 4). We also show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically impaired Plasmodium vivax- and Plasmodium falciparum-infected RBCs.

SUBMITTER: Zhang R 

PROVIDER: S-EPMC4676544 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609.

Zhang Rou R   Suwanarusk Rossarin R   Malleret Benoit B   Cooke Brian M BM   Nosten Francois F   Lau Yee-Ling YL   Dao Ming M   Lim Chwee Teck CT   Renia Laurent L   Tan Kevin Shyong Wei KS   Russell Bruce B  

The Journal of infectious diseases 20150701 1


Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite-infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite's sodium efflux pump (adenosine triphosphate 4). We also show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically impa  ...[more]

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