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

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

doi:10.1021/ci2001764

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

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

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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.

Original language	English (US)
Pages (from-to)	3005-3016
Number of pages	12
Journal	Journal of Chemical Information and Modeling
Volume	51
Issue number	11
DOIs	https://doi.org/10.1021/ci2001764
State	Published - Oct 28 2011
Externally published	Yes

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): KUK-I1-012-43
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".
This publication acknowledges KAUST support, but has no KAUST affiliated authors.

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10.1021/ci2001764

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title = "Identification of the Schistosoma mansoni Molecular Target for the Antimalarial Drug Artemether",

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. {\textcopyright} 2011 American Chemical Society.",

author = "Rosalba Lepore and Silvia Simeoni and Domenico Raimondo and Antonia Caroli and Anna Tramontano and Allegra Via",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): KUK-I1-012-43 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{"}. This publication acknowledges KAUST support, but has no KAUST affiliated authors.",

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AU - Tramontano, Anna

AU - Via, Allegra

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): KUK-I1-012-43 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". This publication acknowledges KAUST support, but has no KAUST affiliated authors.

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N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

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