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Unveiling Taenia solium kinome profile and its potential for new therapeutic targets

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posted on 2020-01-29, 14:10 authored by Naina Arora, Anand Raj, Farhan Anjum, Rimanpreet Kaur, Suraj Singh Rawat, Rajiv Kumar, Shweta Tripathi, Gagandeep Singh, Amit Prasad

Background: Helminth infections cause widespread morbidity and are a significant global disease burden. One among them is Neurocysticercosis, a central nervous system infection caused by the larvae Taenia solium, leading to epilepsy. Helminths are strong immune modulators and can survive for a long time in adverse host environments. Kinases are molecular switches and are essential to initiate/propagate signaling cascades and are detrimental to the regulation of homeostasis. They have been implicated in the progression of many diseases and are potentially lucrative drug targets.

Objective: To identify kinases in T. solium proteome and prioritize them as drug targets.

Methodology: A Hidden Markov Model (HMM) was used to curate and classify kinases into families based on sequence homology to model organisms followed by phylogenetic analysis of each family. To predict potential drug targets, kinases were identified based on a homologically lethal relationship to C. elegans but non-lethal to humans. Kinases thus selected were searched for matching ligands in SARFkinase and DrugBank databases.

Result and conclusion: T. solium kinases make up 1.8% of its proteome, CMGC is the largest kinase family and RGC is the smallest and catalytically inactive family. We predict 23-potential kinases to be drug targets for T. solium.

Funding

N. Arora, R. Kumar and F. Anjum are supported by PhD studentship from the Indian Institute of Technology Mandi. A. Prasad and S. Tripathi acknowledge financial support from Ramalingaswami Fellowship, Department of Biotechnology, Government of India, New Delhi, and SSR is having Junior Research fellowship from Department of Biotechnology, Government of India, New Delhi. A. Prasad is supported through research grants [BT/PR26841/MED/122/121/2017] Department of Biotechnology, Government of India, New Delhi and [ECR/2016/000817/LS] from SERB, New Delhi.

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