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Research Articles

Structure-based drug target prioritisation and rational drug design for targeting Chlamydia trachomatis eye infections

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Pages 3131-3143 | Received 01 Jul 2019, Accepted 27 Jul 2019, Published online: 12 Aug 2019
 

Abstract

Chlamydia trachomatis (C.t) is a major causative of infectious blindness in world. It is a real challenge to combat Chlamydial infection as it is an intracellular pathogen. Hence, it is essential to determine the most potential targets of C.t in order to inhibit or suppress its virulence during its infectious phase. Thus, in this study, the highly expressed-cum-most essential genes reported through our earlier study were reprioritized by structure-based comparative binding site analysis with host proteome. Therefore, computational approaches involving molecular modelling, large-scale binding site prediction and comparison, molecular dynamics simulation studies were performed to narrow down the most potential targets. Furthermore, high-throughput virtual screening and ADMETox were also performed to identify potential hits that shall efficiently inhibit the prioritised targets. Hence, by this study we report Pyruvoyl-dependent arginine decarboxylase (PvlArgDC), DNA-repair protein (RecO) and porin (outer membrane protein) as the most viable targets of C.t which can be potentially targeted by compounds, NSC_13086, MFCD00276409, MFCD05662003, respectively.

Abbreviations
C.t=

Chlamydia trachomatis

STD=

Sexually transmitted disease

HTVS=

High-throughput virtual screening

ADMETox=

Absorption, Distribution, Metabolism, Excretion and Toxicity

PM=

PocketMatch

MD=

Molecular Dynamics simulation

SP=

Standard precision

XP=

Extra precision

MMGBSA=

Molecular mechanics energies combined with generalised Born and surface area continuum solvation

OMP=

Outer membrane protein

PvlArgDC=

Pyruvoyl-dependent arginine decarboxylase

RecO=

Recombination protein O.

Communicated by Ramaswamy H. Sarma

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This article was the part of the study supported by DST-SERB under YSS scheme [File No. YSS/2014/000282].

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