Copper transporter protein (MctB) as a therapeutic target to elicit antimycobacterial activity against tuberculosis

Abstract

Tuberculosis (TB) is a prehistoric infection and major etiologic agent of TB, Mycobacterium tuberculosis, which is considered to have advanced from an early progenitor species found in Eastern Africa. By the 1800s, there were approximately 800 to 1000 fatality case reports per 100,000 people in Europe and North America. This research suggests an In-silico study to identify potential inhibitory compounds for the target Mycobacterial copper transport protein (Mctb). ADME-based virtual screening, molecular docking, and molecular dynamics simulations were conducted to find promising compounds to modulate the function of the target protein. Four chemical compounds, namely Anti-MCT1, Anti-MCT2, Anti-MCT3 and Anti-MCT4 out of 1500 small molecules from the Diverse-lib of MTiOpenScreen were observed to completely satisfy Lipinski rule of five and Veber’s rule. Further, significantly steady interactions with the MctB target protein were observed. Docking experiments have presented 9 compounds with less than −9.0 kcal/mol free binding energies and further MD simulation eventually gave 4 compounds having potential interactions and affinity with target protein and favorable binding energy ranging from −9.2 to −9.3 kcal/mol. We may propose these compounds as an effective candidate to reduce the growth of M. tuberculosis and may also assist present a novel therapeutic approach for Tuberculosis. In vivo and In vitro validation would be needed to proceed further in this direction.

Communicated by Ramaswamy H. Sarma

Keywords:

• TB treatment
• mycobacterial copper transport protein
• molecular dynamics simulations
• PubChem BioAssay database
• molecular docking

Acknowledgement

MD acknowledge the DST-INSPIRE Faculty award, 2017 (IFA17-LSPA82), Govt. of India.

Disclosure statement

No potential conflict of interest was reported by the authors.

Consent to participate

All authors have given their consent to participate in this work.

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All authors have given their consent to publish this work.

Author’s contribution

MD has designed and conceptualized the work. Experiments were done by SJ, SV and MG. DK and RR prepared the input files for molecular dynamics simulation runs and performed molecular dynamics calculations. MD and DK analyzed the simulation results. Manuscript was written by MD, SJ and MG. SJ and SV contributed to experimentation, result analysis and manuscript editing.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.