Computational study of some amoebicidal phytochemicals against heat shock protein of Naegleria fowleri Zarrin Basharat ⁎, Shumaila Zaib, Azra Yasmin Microbiology & Biotechnology Research Lab, Department of Environmental Sciences, Fatima Jinnah Women University, Rawalpindi 46000, Pakistan abstract article info Article history: Received 13 September 2016 Accepted 13 September 2016 Available online xxxx Naegleria fowleri (commonly known as brain eating amoeba) is a causative agent of brain infection known as naegleriasis or primary amoebic meningoencephalitis. Structure based computational screening for searching potent antiamoebic phytochemicals against the target heat shock protein (Hsp) was attempted. It is a quick method for discovery of inhibitors against the therapeutic target of interest. A set of eleven amoebicidal mole- cules were screened against Hsp70 of brain eating amoeba. Hsp70 was chosen becauseit plays an imperative role in protein folding, protection from stress and regulation of cell machinery, and may serve as a good drug tar- get. Structure based virtual screening indicated bergenin and (-)-epigallocatechin gallate (EGCG) as most potent binders of this protein. These compounds need to be further tested for obtaining detailed insights. © 2016 Elsevier Inc. All rights reserved. Keywords: Brain eating amoeba Naegleria fowleri Virtual screening Docking Phytochemicals Hsp70 1. Introduction Naegleria fowleri is a free living protist which belongs to phylum Percolozoa (Angrup et al., 2010). It is mostly found in fresh water bodies i.e. ponds, rivers, lakes and hot springs (De Jonckheere, 2011). Beside fresh water bodies, it also occurs in the soil near warm-water discharge sites of industrial plants. N. fowleri is commonly known as brain eating amoeba as it attacks the brain. It invades the central nervous system by passing through the nose (the olfactory mucosa and cribriform plate), and results in primary amoebic meningoencephalitis (PAM) (Khan and Ahmad, 2015). This infection is unusual but fatal, fatality rate greater than 95% is reported. Cases have been reported from several countries including Pakistan (Mahmood, 2015). PAM is much destruc- tive, rapidly spreading and lack effective treatments. Amphotericin B proved effective against PAM in vitro, but when test- ed on people after contraction of PAM, less than 1% survival rate was re- corded. Two other drugs, Chlorpromazine and B. Miltefosine are under trial (Kim et al., 2008), but is not known that whether these antibiotics will produce a beneficial result against PAM, or not. Also there is no vac- cine to protect against N. fowleri infection (Khan and Ahmad, 2015). In order to prevent and treat PAM, new or improved drugs are required. For the identification of specific drug targets, the drug discovery and de- velopmental process shifted to computational approaches like comparative genomics, molecular docking and virtual screening (Bredel and Jacoby, 2004; Kitchen et al., 2004; Ghosh et al., 2006). In this study, quick method of drug discovery process i.e. structure based virtual screening has been used. Drug targets plays fundamental role in the development and design of new drug. One such drug target present in N. fowleri is Hsp70. This protein exists in all organisms and aids folding of synthesized proteins (Basharat, 2015). Hsp of parasites is classified as having immune- dominant antigens and considered as potential drug target (Kumar et al., 2007; Evans et al., 2010; Pallavi et al., 2010; Shahinas et al., 2010). This peptide plays major role in the survival, proliferation and pathogenicity of N. fowleri (Song et al., 2008). The important functions of Hsp70 are protein folding, refolding of denatured proteins and regu- lation of immune mechanism of host (Segal et al., 2006; Shonhai, 2010). Therefore to hinder the survival and growth of this amoeba, inhibition of Hsp70 is essential which prevents N. fowleri proliferation and pro- vides a target for developing antiamoebic drug. Plants constitute chemicals with medicinal properties and have been used as remedy for several diseases since long time. Phytochemicals constitute a lot of drug formulations as they can carry out therapeutic actions for lot of diseases ranging from dysentery (Otshudi et al., 2000) to cardio oncological diseases (Ferrari et al., 2011) and beyond. They could act as anti-inflammatory, anti-cancer, anti-malarial, anti- constipative, anti-viral, anti-bacterial, insecticide as well as inhibit cho- lesterol synthesis (Begum et al., 2015). Phytochemicals are valuable as they do not pose the threat of antibiotic resistance (Chatterjee et al., 2016). In the present study, computational docking was attempted to screen potent amoebicidals against Hsp70 and their interaction with the receptor protein was mapped with MOE. Gene Reports xxx (2016) xxx–xxx Abbreviations: Hsp, heat shock protein; PAM, primary amoebic meningoencephalitis; MOE, molecular Operating Environment; EGCG, (-)-epigallocatechin gallate. ⁎ Corresponding author. E-mail address: zarrin.iiui@gmail.com (Z. Basharat). GENREP-00069; No of Pages 5 http://dx.doi.org/10.1016/j.genrep.2016.09.003 2452-0144/© 2016 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Gene Reports journal homepage: www.elsevier.com/locate/genrep Please cite this article as: Basharat, Z., et al., Computational study of some amoebicidal phytochemicals against heat shock protein of Naegleria fowleri, Gene Reports (2016), http://dx.doi.org/10.1016/j.genrep.2016.09.003