Human Aurora kinase inhibitor Hesperadin reveals epistatic interaction between Plasmodium falciparum PfArk1 and PfNek1 kinases

Commun Biol. 2020 Nov 20;3(1):701. doi: 10.1038/s42003-020-01424-z.


Mitosis has been validated by numerous anti-cancer drugs as being a druggable process, and selective inhibition of parasite proliferation provides an obvious opportunity for therapeutic intervention against malaria. Mitosis is controlled through the interplay between several protein kinases and phosphatases. We show here that inhibitors of human mitotic kinases belonging to the Aurora family inhibit P. falciparum proliferation in vitro with various potencies, and that a genetic selection for mutant parasites resistant to one of the drugs, Hesperadin, identifies a resistance mechanism mediated by a member of a different kinase family, PfNek1 (PF3D7_1228300). Intriguingly, loss of PfNek1 catalytic activity provides protection against drug action. This points to an undescribed functional interaction between Ark and Nek kinases and shows that existing inhibitors can be used to validate additional essential and druggable kinase functions in the parasite.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinases* / antagonists & inhibitors
  • Aurora Kinases* / chemistry
  • Aurora Kinases* / metabolism
  • Epistasis, Genetic* / drug effects
  • Epistasis, Genetic* / genetics
  • Humans
  • Indoles / pharmacology*
  • NIMA-Related Kinase 1* / chemistry
  • NIMA-Related Kinase 1* / genetics
  • NIMA-Related Kinase 1* / metabolism
  • Plasmodium falciparum* / drug effects
  • Plasmodium falciparum* / growth & development
  • Plasmodium falciparum* / metabolism
  • Protozoan Proteins / antagonists & inhibitors
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / metabolism
  • Sulfonamides / pharmacology*


  • Indoles
  • Protozoan Proteins
  • Sulfonamides
  • Aurora Kinases
  • NIMA-Related Kinase 1
  • hesperadin