Genome analysis of Chlamydia trachomatis for functional characterization of hypothetical proteins to discover novel drug targets

Naqvi, Ahmad Abu Turab; Rahman, Safikur; Rubi,; Zeya, Firdaus; Kumar, Kundan; Choudhary, Hani; Jamal, Mohammad Sarwar; Kim, Jihoe; Hassan, Md. Imtaiyaz

doi:10.1016/j.ijbiomac.2016.12.045

Cited by 20 publications

(9 citation statements)

References 68 publications

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“…The predicted virulent proteins may help in spreading of infection and therefore is anticipated as the therapeutic target for drug development against the pathogen. The virulent proteins have been targeted earlier for drug discovery process . The molecular weight and other physiochemical properties of the protein are critical to understand it as the potential therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

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Targeting metabolic pathways proteins of Orientia tsutsugamushi using combined hierarchical approach to combat scrub typhus

Sharma

Verma

et al. 2018

J of Molecular Recognition

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Orientia tsutsugamushi (Ott) is a causative agent of chigger‐borne zoonosis, scrub typhus which is life threatening and highly pervasive illness in humans. In this report, we have mined and classified the proteins involved in pathways unique to Ott by using high‐throughput computational techniques. The 12 metabolic pathways were found to be unique to the pathogen. Forty‐six proteins were reported to be essential for the pathogen's survival and non‐homologous to the humans. The proteins were categorized into different classes, ie, enzymes, transporters, DNA‐binding, secretory, and outer membrane proteins. Further, in silico analysis of 46 proteins showed that 25 proteins were suitable therapeutic targets with known druggable properties. The structural modeling of B3CSG3 (MurA) protein was carried out and catalytic site essential for its functioning was analyzed. Virtual screening of chemical compounds was performed against modeled structure. The docking study by AutodockVina reported compound from PubChem with CID: 16036947 as best and potential inhibitor by means of docking score and binding affinity. The reliability and stability of the MurA‐16036947 complex were confirmed with molecular dynamics simulation. The report will provide insight to understand the mechanism of pathogenesis of Ott and instigate the development of effective treatment strategies against this disease.

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Section: Discussionmentioning

confidence: 99%

“…The virulent proteins have been targeted earlier for drug discovery process. 61,62 The molecular weight and other physiochemical properties of the protein are critical to understand it as the potential therapeutic target. The proteins which have molecular weight < 110 kDa were supposed to be appropriate target.…”

Section: Molecular Dynamics Simulationmentioning

confidence: 99%

Targeting metabolic pathways proteins of Orientia tsutsugamushi using combined hierarchical approach to combat scrub typhus

Sharma

Verma

et al. 2018

J of Molecular Recognition

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“…during blood stage infection revealed about 800 genes that have similar expression patterns across species, among which 240 were demonstrated to be druggable by online drug target prioritization databases ( Hoo et al, 2016 ). Similarly, genomic and transcriptomic analyses have been carried out with other pathogens with encouraging results in fungi ( Kaltdorf et al, 2016 ), bacteria ( Turab Naqvi et al, 2017 ), and viruses ( Dapat and Oshitani, 2016 ).…”

Section: Application Of Omics To Vaccine Target Identification and Drmentioning

confidence: 99%

Highlights on the Application of Genomics and Bioinformatics in the Fight Against Infectious Diseases: Challenges and Opportunities in Africa

et al. 2018

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Genomics and bioinformatics are increasingly contributing to our understanding of infectious diseases caused by bacterial pathogens such as Mycobacterium tuberculosis and parasites such as Plasmodium falciparum. This ranges from investigations of disease outbreaks and pathogenesis, host and pathogen genomic variation, and host immune evasion mechanisms to identification of potential diagnostic markers and vaccine targets. High throughput genomics data generated from pathogens and animal models can be combined with host genomics and patients’ health records to give advice on treatment options as well as potential drug and vaccine interactions. However, despite accounting for the highest burden of infectious diseases, Africa has the lowest research output on infectious disease genomics. Here we review the contributions of genomics and bioinformatics to the management of infectious diseases of serious public health concern in Africa including tuberculosis (TB), dengue fever, malaria and filariasis. Furthermore, we discuss how genomics and bioinformatics can be applied to identify drug and vaccine targets. We conclude by identifying challenges to genomics research in Africa and highlighting how these can be overcome where possible.

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“…Functional characterization of HPs using various structure and sequence-based bioinformatic tools can help in classifying these proteins into diverse functional classes, which can give more insight into their activities, structures, and their roles in the metabolism [33]. Elucidation of roles of these HPs from several pathogenic organisms such as Vibrio cholerae O139, Chlamydia trachomatis, Neisseria meningitidis, Mycobacterium tuberculosis, Haemophilus influenzae, Helicobacter pylori, and others using bioinformatic tools have already been reported [34][35][36][37][38][39].…”

Section: Introductionmentioning

confidence: 99%

Functional Annotation and Curation of Hypothetical Proteins Present in A Newly Emerged Serotype 1c of Shigella flexneri: Emphasis on Selecting Targets for Virulence and Vaccine Design Studies

Sen¹,

Verma²

2020

Genes

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Shigella flexneri is the principal cause of bacillary dysentery, contributing significantly to the global burden of diarrheal disease. The appearance and increase in the multi-drug resistance among Shigella strains, necessitates further genetic studies and development of improved/new drugs against the pathogen. The presence of an abundance of hypothetical proteins in the genome and how little is known about them, make them interesting genetic targets. The present study aims to carry out characterization of the hypothetical proteins present in the genome of a newly emerged serotype of S. flexneri (strain Y394), toward their novel regulatory functions using various bioinformatics databases/tools. Analysis of the genome sequence rendered 4170 proteins, out of which 721 proteins were annotated as hypothetical proteins (HPs) with no known function. The amino acid sequences of these HPs were evaluated using a combination of latest bioinformatics tools based on homology search against functionally identified proteins. Functional domains were considered as the basis to infer the biological functions of HPs in this case and the annotation helped in assigning various classes to the proteins such as signal transducers, lipoproteins, enzymes, membrane proteins, transporters, virulence, and binding proteins. This study contributes to a better understanding of growth, survival, and disease mechanism at molecular level and provides potential new targets for designing drugs against Shigella infection.

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Genome analysis of Chlamydia trachomatis for functional characterization of hypothetical proteins to discover novel drug targets

Cited by 20 publications

References 68 publications

Targeting metabolic pathways proteins of Orientia tsutsugamushi using combined hierarchical approach to combat scrub typhus

Targeting metabolic pathways proteins of Orientia tsutsugamushi using combined hierarchical approach to combat scrub typhus

Highlights on the Application of Genomics and Bioinformatics in the Fight Against Infectious Diseases: Challenges and Opportunities in Africa

Functional Annotation and Curation of Hypothetical Proteins Present in A Newly Emerged Serotype 1c of Shigella flexneri: Emphasis on Selecting Targets for Virulence and Vaccine Design Studies

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