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

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. AbbreviationsC.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.

Chlamydia trachomatis

Sexually transmitted disease

High-throughput virtual screening

Absorption, Distribution, Metabolism, Excretion and Toxicity

PocketMatch

Molecular Dynamics simulation

Standard precision

Extra precision

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

Outer membrane protein

Pyruvoyl-dependent arginine decarboxylase

Recombination protein O.

Communicated by Ramaswamy H. Sarma