Identification of the Schistosoma mansoni Molecular Target for the Antimalarial Drug Artemether

Type
Article

Authors
Lepore, Rosalba
Simeoni, Silvia
Raimondo, Domenico
Caroli, Antonia
Tramontano, Anna
Via, Allegra

KAUST Grant Number
KUK-I1-012-43

Online Publication Date
2011-10-28

Print Publication Date
2011-11-28

Date
2011-10-28

Abstract
Plasmodium falciparum and Schistosoma mansonii are the parasites responsible for most of the malaria and schistosomiasis cases in the world. Notwithstanding their many differences, the two agents have striking similarities in that they both are blood feeders and are targets of an overlapping set of drugs, including the well-known artemether molecule. Here we explore the possibility of using the known information about the mode of action of artemether in Plasmodium to identify the molecular target of the drug in Schistosoma and provide evidence that artemether binds to SmSERCA, a putative Ca2+-ATPase of Schistosoma. We also predict the putative binding mode of the molecule for both its Plasmodium and Schistosoma targets. Our analysis of the mode of binding of artemether to Ca2+-ATPases also provides an explanation for the apparent paradox that, although the molecule has no side effect in humans, it has been shown to possess antitumoral activity. © 2011 American Chemical Society.

Citation
Lepore R, Simeoni S, Raimondo D, Caroli A, Tramontano A, et al. (2011) Identification of the Schistosoma mansoni Molecular Target for the Antimalarial Drug Artemether. J Chem Inf Model 51: 3005–3016. Available: http://dx.doi.org/10.1021/ci2001764.

Acknowledgements
We thank all our colleagues of the Biocomputing Unit and the members of the Fondazione Roma Research Unit led by Prof. Maurizio Brunori for useful discussions. This work was partially supported by award number KUK-I1-012-43 made by King Abdullah University of Science and Technology (KAUST), Human Frontier Science Program HFSP-RGP0054/2006-C grant (http://www.hfsp.org/), FIRB Italbionet and Proteomica, Ministery of Health grant contract no. Onc_Ord 25/07, Fondazione Roma, and the IIT SEED project "Advanced Computational Methods for Biophysics, Drug Design, and Energy Research".

Publisher
American Chemical Society (ACS)

Journal
Journal of Chemical Information and Modeling

DOI
10.1021/ci2001764

PubMed ID
21995318

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