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Identification of inhibitors of Plasmodium falciparum RuvB1 helicase using biochemical assays

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Abstract

Human malaria is a major parasitic infection, and the situation has worsened mainly due to the emergence of resistant malaria parasites to several anti-malarial drugs. Thus, an urgent need to find suitable drug targets has led to the development of newer classes of anti-malarial drugs. Helicases have been targeted to develop therapeutics for viral, bacterial, and other microorganism infections. Recently, Plasmodium falciparum RuvB ATPases/helicases have been characterized and proposed as a suitable antimalarial drug target. In the present study, the screening of various compounds was done and the results suggest that PfRuvB1 ATPase activity is inhibited considerably by the novobiocin and partially by cisplatin and ciprofloxacin. Helicase assay of PfRuvB1 in the presence of various compounds suggest novobiocin, actinomycin, and ethidium bromide as potent inhibitors. Novobiocin inhibits the helicase activity of PfRuvB1 possibly by blocking the ATPase activity of PfRuvB1. This study is unique in respect to the identification of novobiocin as inhibitor of PfRuvB1, partially by competing with ATP binding at its active site and provides evidence for PfRuvB1 as target of novobiocin after DNA gyrase-B and HSP90. These studies will certainly help the pharmacologist to design and develop some novel inhibitor specific to PfRuvB1, which may serve as suitable chemotherapeutics to target malaria.

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Acknowledgments

This work is partially supported by the Department of Biotechnology and Department of Science and Technology grants. Infrastructural support from the Department of Biotechnology, Government of India is gratefully acknowledged.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Malaria Group, International Centre for Genetic Engineering and Biotechnology, P.O. Box 10504, Aruna Asaf Ali Marg, New Delhi, 110067, India

    Moaz Ahmad, Mohammed Tarique, Narendra Tuteja & Renu Tuteja

  2. Department of Biotechnology, Jamia Hamdard, Hamdard Nagar, New Delhi, India

    Farhat Afrin

Authors
  1. Moaz Ahmad
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  2. Mohammed Tarique
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  3. Farhat Afrin
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  4. Narendra Tuteja
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  5. Renu Tuteja
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Corresponding author

Correspondence to Renu Tuteja.

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Handling Editor: Reimer Stick

Moaz Ahmad and Mohammed Tarique contributed equally to this work.

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Ahmad, M., Tarique, M., Afrin, F. et al. Identification of inhibitors of Plasmodium falciparum RuvB1 helicase using biochemical assays. Protoplasma 252, 117–125 (2015). https://doi.org/10.1007/s00709-014-0664-6

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  • DOI: https://doi.org/10.1007/s00709-014-0664-6

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