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Structure-Based Screening of DNA GyraseB Inhibitors for Therapeutic Applications in Tuberculosis: a Pharmacoinformatics Study

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Abstract

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB) and considered as serious public health concern worldwide which kills approximately five thousand people every day. Therefore, TB drug development efforts are in gigantic need for identification of new potential chemical agents to eradicate TB from the society. The bacterial DNA gyrase B (GyrB) protein as an experimentally widely accepted effective drug target for the development of TB chemotherapeutics. In the present study, advanced pharmacoinformatics approaches were used to screen the Mcule database against the GyrB protein. Based on a number of chemometric parameters, five molecules were found to be crucial to inhibit the GyrB. A number of molecular binding interactions between the proposed inhibitors and important active site residues of GyrB were observed. The predicted drug-likeness properties of all molecules were indicated that compounds possess characteristics to be the drug-like candidates. The dynamic nature of each molecule was explored through the molecular dynamics (MD) simulation study. Various analyzing parameters from MD simulation trajectory have suggested rationality of the molecules to be potential GyrB inhibitor. Moreover, the binding free energy was calculated from the entire MD simulation trajectories highlighted greater binding free energy values for all newly identified compounds also substantiated the strong binding affection towards the GyrB in comparison to the novobiocin. Therefore, the proposed molecules might be considered as potential anti-TB chemical agents for future drug discovery purposes subjected to experimental validation.

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Acknowledgments

The authors would like to extend their sincere appreciation to the Researchers Supporting Project for funding this work through Research Number (RSP-2020/138), King Saud University, Riyadh, Saudi Arabia.

Funding

The authors would like to extend their sincere appreciation to the Researchers Supporting Project for funding this work through Research Number (RSP-2019/138), King Saud University, Riyadh, Saudi Arabia.

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Author notes

  1. Pranjali Mahadeo Tambe and Shovonlal Bhowmick contributed equally and can be considered as the first author.

Authors and Affiliations

  1. Department of Bioinformatics, Rajiv Gandhi Institute of IT and Biotechnology, Bharati Vidyapeeth Deemed University, Pune-Satara Road, Pune, India

    Pranjali Mahadeo Tambe & Preeti Chunarkar Patil

  2. Department of Chemical Technology, University of Calcutta, 92 A.P.C. Road, Kolkata, India

    Shovonlal Bhowmick

  3. Faculty of Pharmacy, DIT University, Mussoorie-Diversion Road, Makkawala, Dehradun, Uttarakhand, 248009, India

    Sushil K. Chaudhary

  4. Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    Mohammad Rizwan Khan, Saikh M. Wabaidur & Mohd. Muddassir

  5. Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, M13 9PL, UK

    Md Ataul Islam

  6. School of Health Sciences, University of Kwazulu-Natal, Westville Campus, Durban, South Africa

    Md Ataul Islam

  7. Department of Chemical Pathology, Faculty of Health Sciences, University of Pretoria and National Health Laboratory Service Tshwane Academic Division, Pretoria, South Africa

    Md Ataul Islam

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  1. Pranjali Mahadeo Tambe
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  2. Shovonlal Bhowmick
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Contributions

Pranjali Mahadeo Tambe: data curation, investigation and methodology; Shovonlal Bhowmick: research conceptualization, investigation and methodology, supervison, writing—review and editing; Sushil K. Chaudhary: research conceptualization, writing—review and editing; Mohammad Rizwan Khan: writing—review and editing; Saikh M Wabaidur: writing—review and editing; Mohd. Muddassir: research conceptualization, writing—review and editing; Preeti Chunarkar Patil: research conceptualization, writing—review and editing; Md Ataul Islam: research conceptualization, investigation and methodology, supervison, writing—review and editing

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Correspondence to Md Ataul Islam.

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Tambe, P.M., Bhowmick, S., Chaudhary, S.K. et al. Structure-Based Screening of DNA GyraseB Inhibitors for Therapeutic Applications in Tuberculosis: a Pharmacoinformatics Study. Appl Biochem Biotechnol 192, 1107–1123 (2020). https://doi.org/10.1007/s12010-020-03374-y

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