This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Dr. Manish Dwivedi
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow-226028, India
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5217-9039
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This work is licensed under a CC BY 4.0 License. Read Full License
Declarations:
Declarations
- The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
Tuberculosis (TB) is a serious communicative disease caused by a bacterium named Mycobacterium tuberculosis. Albeit there are vaccines and drugs available to treat the disease, Multidrug-resistant TB (MDR-TB) is still one of the most critical challenges for the investigators where the development of efflux systems makes them resistant to drugs. Tap is a multidrug efflux pump and proposed to have a significant role in the survival of M. tuberculosis making it drug-resistant. In the present study, we have utilized various In silico approaches to predict the applicability of FDA approved ion channel inhibitors and blockers as therapeutic leads against Tuberculosis. We have analysed 18 inhibitor compounds and eventually screened three ligands as drugs, Glibenclimide, Lubiprostone and Flecainde that have displayed the novel stable binding with Tap protein aiming to affect or inhibit its activity. Structure of Tap protein is predicted by Phyre2 server followed by its characterization by 10ns MD simulations using the CABS-flex 2.0 server and validation by Ramachandran plot. PyRx software presented the binding affinity varied in the range of -8.00 kcal/mol to -9.8 kcal/mol, implies that the drug molecules can spontaneously interact with the target protein. Amongst them, Glibenclimide shows the highest binding affinity with ΔG of -9.8 kcal/mol. This study proposed Tap protein as an interesting drug target and investigated drugs may show considerable effects on the target protein showing a novel therapeutic lead against Tuberculosis.
Keywords
Mycobacterium tuberculosis, Tap, homology modelling, MD simulations, molecular docking, drug repurposing
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Dr. Manish Dwivedi
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow-226028, India
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5217-9039
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 30 Dec, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Declarations:
Declarations
- The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
Tuberculosis (TB) is a serious communicative disease caused by a bacterium named Mycobacterium tuberculosis. Albeit there are vaccines and drugs available to treat the disease, Multidrug-resistant TB (MDR-TB) is still one of the most critical challenges for the investigators where the development of efflux systems makes them resistant to drugs. Tap is a multidrug efflux pump and proposed to have a significant role in the survival of M. tuberculosis making it drug-resistant. In the present study, we have utilized various In silico approaches to predict the applicability of FDA approved ion channel inhibitors and blockers as therapeutic leads against Tuberculosis. We have analysed 18 inhibitor compounds and eventually screened three ligands as drugs, Glibenclimide, Lubiprostone and Flecainde that have displayed the novel stable binding with Tap protein aiming to affect or inhibit its activity. Structure of Tap protein is predicted by Phyre2 server followed by its characterization by 10ns MD simulations using the CABS-flex 2.0 server and validation by Ramachandran plot. PyRx software presented the binding affinity varied in the range of -8.00 kcal/mol to -9.8 kcal/mol, implies that the drug molecules can spontaneously interact with the target protein. Amongst them, Glibenclimide shows the highest binding affinity with ΔG of -9.8 kcal/mol. This study proposed Tap protein as an interesting drug target and investigated drugs may show considerable effects on the target protein showing a novel therapeutic lead against Tuberculosis.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
This is a list of supplementary files associated with this preprint. Click to download.
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