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. 2017 Sep;6(3):113-122.
doi: 10.22099/mbrc.2017.4084.

Assessment of vocation of rifabutin and rifapentine in replace of rifampcin in drug resistance leprosy patients: a molecular simulation study

Partha Sarathi Mohanty  1 , Farah Naaz  1 , Avi Kumar Bansal  2 , Umesh Datta Gupta  3
Affiliations

Assessment of vocation of rifabutin and rifapentine in replace of rifampcin in drug resistance leprosy patients: a molecular simulation study

Partha Sarathi Mohanty et al. Mol Biol Res Commun. 2017 Sep.

Abstract

The emergence of drug resistance in leprosy is a major hurdle in leprosy elimination programme. Although the problem of drug resistance is presently not acute, it is important that we collect data more systematically and monitor the trend carefully so that effective measures to combat this problem can be developed. The present study aimed at the explication of cross resistance of rifabutin and rifapentine to rifampicin which would be helpful to programme managers for implementing rifabutin or rifapentine in replace of rifampicin. In this study we built 3D model of the M. leprae rpoB using Swiss Model and the modelled structure was docked with rifampicin, rifabutin and rifapentine. We established that these 3 antibiotics interact with the same binding region in the modelled rpoB of M. leprae. Thus we conclude that vocation of rifabutin and rifapentine could not be suitable in replace of rifampicin to combat with drug resistance leprosy.

Keywords: Docking; Drug resistance; Leprosy; Rifabutin; Rifampicin; Rifapentine.

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Figures

Figure 1
Figure 1
2D structure of rifampicin (A), 2D structure of rifabutin (B), 2D structure of rifapentine (C
Figure 2
Figure 2
Predicted model of M. leprae rpoB, where helical regions represent the alpha helices and wire-like regions represent the loops
Figure 3
Figure 3
Ramachandran plot of predicted 3D structure of M. leprae rpoB showing the amino acid plots in most favoured regions, additional allowed region and generously allowed regions
Figure 4
Figure 4
Protein Structure Analysis (ProSA) of modelled rpoB (A) Overall quality of 4KBM showing a z-score of -10.56 (Native conformation to its template). (B) Overall quality of template (4KBM) model showing a z-score of -11.32
Figure 5
Figure 5
Molecular interaction of modelled rpoB with drug molecules (A, B: with rifampicin, C, D: with rifabutin, E, F: with rifapentine
See this image and copyright information in PMC

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