Human malaria parasite cold shock protein plays an essential role in asexual and sexual stage development and presents an excellent druggable target

Cold shock proteins are well characterized in bacteria, plants and humans, however there is no information on their existence and role in malaria parasite. Here, we have delineated the function of a novel cold shock protein of Plasmodium falciparum ( Pf ) which we have annotated ‘ Pf CoSP’. Our results show that recombinant Pf CoSP has both DNA and RNA binding activity, and also interacts with alpha and beta tubulin of Pf. Pf CoSP binds with RNA and alpha tubulin simultaneously to form a complex. Expression of Pf CoSP was found during asexual blood stages and gametocyte stages of malaria parasite. Pf CoSP expression up-regulates many folds upon cold treatment, suggesting its role during hypothermic cold shock. Interestingly, Pf CoSP showed binding with human cold shock protein LIN28A inhibitor ‘LI71’ that also inhibits Pf CSP -alpha/beta tubulin interactions. LI71 showed antimalarial activity against asexual blood stage and gametocyte stage suggesting its multi-stage, transmission-blocking potential. We propose that Pf CoSP may form a workbench for translation during cold stress via its interactions with target mRNAs and the cytoskeleton protein tubulin. ### Competing Interest Statement The authors have declared no competing interest.