Article
A G358S mutation in the Plasmodium falciparum Na+ pump PfATP4 confers clinically-relevant resistance to cipargamin.
Nature communications - 30 Sept 2022
Qiu Deyun, Pei Jinxin V, Rosling James E O, Thathy Vandana, Li Dongdi, Xue Yi, Tanner John D, Penington Jocelyn Sietsma, Aw Yi Tong Vincent, Aw Jessica Yi Han, Xu Guoyue, Tripathi Abhai K, Gnadig Nina F, Yeo Tomas, Fairhurst Kate J, Stokes Barbara H, Murithi James M, Kümpornsin Krittikorn, Hasemer Heath, Dennis Adelaide S M, Ridgway Melanie C, Schmitt Esther K, Straimer Judith, Papenfuss Anthony T, Lee Marcus C S, Corry Ben, Sinnis Photini, Fidock David A, van Dooren Giel G, Kirk Kiaran, Lehane Adele M
Abstract excerpt
Diverse compounds target the Plasmodium falciparum Na+ pump PfATP4, with cipargamin and (+)-SJ733 the most clinically-advanced. In a recent clinical trial for cipargamin, recrudescent parasites emerged, with most having a G358S mutation in PfATP4. Here, we show that PfATP4G358S parasites can withstand micromolar concentrations of cipargamin and (+)-SJ733, while remaining susceptible to antimalarials that do not...
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