Volume 6 Supplement 1

9th German Conference on Chemoinformatics

Open Access

Identification of host interactions for phenotypic antimalarial hits

Journal of Cheminformatics20146(Suppl 1):O12

DOI: 10.1186/1758-2946-6-S1-O12

Published: 11 March 2014

Malaria is one of the most epidemic infectious diseases in the world affecting millions of patients and causing more than 500,000 deaths each year. Although there are several established antimalarials in clinical use, there is an urgent need for new drugs due to rapid resistance development. In recent years, more than 20,000 hits phenotypically active against P. falciparum, one of the major malaria causing agents, were disclosed from three independent HTS campaigns [13]. In order to make these hit libraries accessible to as many biological laboratories as possible, the MMV compiled and distributed the Open Access Malaria Box, a set of 400 chemically diverse active compounds [4]. One important task is now to elucidate the mode of action of those compounds. However, beside the parasite targets it is also necessary to identify potential host interactions in order to anticipate the risk of undesired side effects of those chemotypes at the earliest possible stage of development.

To this end, we applied a ligand-based virtual target profiling approach to predict possible interactions with human targets [5]. Amongst others, kinases and GPCRs were identified as the most important target classes. Subsequently, several hundred predicted interactions were selected for prospective experimental testing. Results showed that a substantial part of the Malaria Box exhibits the potential of interacting with human GPCRs. To this extent, this was unexpected beforehand since the pathogenic agent does not contain any GPCRs. In this respect, particular attention was given to 5-HT2B receptor agonism, an effect associated to cardiac valvulopathy [6].

Authors’ Affiliations

Chemotargets SL and Systems Pharmacology Group, Research Programme on Biomedical Informatics (GRIB), IMIM Hospital del Mar Research Institute and Universitat Pompeu Fabra, Parc de Recerca Biomèdica


  1. Gamo FJ, et al: Thousands of chemical starting points for antimalarial lead identification. Nature. 2010, 465: 305-310. 10.1038/nature09107.View ArticleGoogle Scholar
  2. Guiguemde WA, et al: Chemical genetics of Plasmodium falciparum. Nature. 2010, 465: 311-315. 10.1038/nature09099.View ArticleGoogle Scholar
  3. Plouffe D, et al: In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen. Proc Natl Acad Sci. 2008, USA, 105: 9059-9064. 10.1073/pnas.0802982105.Google Scholar
  4. Spangenberg T, et al: The open access malaria box: a drug discovery catalyst for neglected diseases. PLoS ONE. 2013, 8: e62906-10.1371/journal.pone.0062906.View ArticleGoogle Scholar
  5. PredictFX v12.3. Chemotargets SL, Barcelona
  6. Roth B: Drugs and valvular heart disease. N Engl J Med. 2007, 356: 6-9. 10.1056/NEJMp068265.View ArticleGoogle Scholar


© Spitzmüller and Mestres; licensee Chemistry Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.