Computational Identification and Screening of Natural Compounds as Drug Targets against the Fish Pathogen, Pseudomonas fluorescens

Murali, S.; Jahageerdar, Shrinivas; Kumar, Sanath; Krishna, Gopal

doi:10.20546/ijcmas.2017.611.413

Cited by 1 publication

(1 citation statement)

References 32 publications

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“…The essential proteins of M. tuberculosis H37Rv were predicted through the Database of Essential Gene (DEG) server v15.2 [58], which contains 53,885 essential genes and 786 essential non-cod- ing sequences. This server is broadly used in the subtractive genomics/proteomics approach to identify essential proteins in organisms [59][60][61]. The protein hit settings of an expectation value (E-value) ≤ 10 -100 , identity ≥ 25%, and bit score > 100 were used to filter essential proteins for this pathogen [57,62].…”

Section: Screening Of Essential Proteinsmentioning

confidence: 99%

Multi-epitope vaccine against drug-resistant strains of Mycobacterium tuberculosis: a proteome-wide subtraction and immunoinformatics approach

Khan,

Mahmud,

Islam

et al. 2023

Genomics Inform

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Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Toll-like receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

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