Target-similarity search using Plasmodium falciparum proteome identifies approved drugs with anti-malarial activity and their possible targets

PloS One
Reagan M MogireSteven G Nyanjom

Abstract

Malaria causes about half a million deaths annually, with Plasmodium falciparum being responsible for 90% of all the cases. Recent reports on artemisinin resistance in Southeast Asia warrant urgent discovery of novel drugs for the treatment of malaria. However, most bioactive compounds fail to progress to treatments due to safety concerns. Drug repositioning offers an alternative strategy where drugs that have already been approved as safe for other diseases could be used to treat malaria. This study screened approved drugs for antimalarial activity using an in silico chemogenomics approach prior to in vitro verification. All the P. falciparum proteins sequences available in NCBI RefSeq were mined and used to perform a similarity search against DrugBank, TTD and STITCH databases to identify similar putative drug targets. Druggability indices of the potential P. falciparum drug targets were obtained from TDR targets database. Functional amino acid residues of the drug targets were determined using ConSurf server which was used to fine tune the similarity search. This study predicted 133 approved drugs that could target 34 P. falciparum proteins. A literature search done at PubMed and Google Scholar showed 105 out of the 133 drug...Continue Reading

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Citations

Nov 12, 2019·Briefings in Bioinformatics·Francis E AgamahEmile R Chimusa
Jul 1, 2020·Antimicrobial Agents and Chemotherapy·Letícia Tiburcio FerreiraFabio Trindade Maranhão Costa
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Apr 10, 2019·Journal of Medicinal Chemistry·Thomas ChevietSuzanne Peyrottes

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Methods Mentioned

BETA
deamination

Software Mentioned

GraphPad
ConSurf server
R
STITCH
GraphPad Prism
Windows
ChEMBL
MODEL
BLAST
Google Scholar

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Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.