Publications by authors named "Mohammad Uzzal Hossain"

20 Publications

  • Page 1 of 1

Novel mutations in NSP-1 and PLPro of SARS-CoV-2 NIB-1 genome mount for effective therapeutics.

J Genet Eng Biotechnol 2021 Apr 2;19(1):52. Epub 2021 Apr 2.

Molecular Biotechnology Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka, 1349, Bangladesh.

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), is rapidly acquiring new mutations. Analysis of these mutations is necessary for gaining knowledge regarding different aspects of therapeutic development. Previously, we have reported a Sanger method-based genome sequence of a viral isolate named SARS-CoV-2 NIB-1, circulating in Bangladesh. The genome has four novel non-synonymous mutations in V121D, V843F, A889V, and G1691C positions.

Results: Using different computational tools, we have found V121D substitution has the potential to destabilize the non-structural protein-1 (NSP-1). NSP-1 inactivates the type-1 interferon-induced antiviral system. Hence, this mutant could be a basis of attenuated vaccines against SARS-CoV-2. V843F, A889V, and G1691C are all located in nonstructural protein-3 (NSP-3). G1691C can decrease the flexibility of the protein. V843F and A889V might change the binding pattern and efficacy of SARS-CoV-2 papain-like protease (PLPro) inhibitor GRL0617. V843F substitution in PLPro was the most prevalent mutation in the clinical samples. This mutation showed a reduced affinity for interferon-stimulated gene-15 protein (ISG-15) and might have an impact on innate immunity and viral spread. However, V843F+A889V double mutant exhibited the same binding affinity as wild type PLPro. A possible reason behind this phenomenon can be that V843F is a conserved residue of PLPro which damaged the protease structure, but A889V, a less conserved residue, presumably neutralized that damage.

Conclusions: Mutants of NSP-1 could provide attenuated vaccines against coronavirus. Also, these mutations of PLPro might be targeted to develop better anti-SARS therapeutics. We hope our study will help to get better insides during the development of attenuated vaccine and PLPro inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s43141-021-00152-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017899PMC
April 2021

Evaluation of the susceptibility and fatality of lung cancer patients towards the COVID-19 infection: A systemic approach through analyzing the ACE2, CXCL10 and their co-expressed genes.

Curr Res Microb Sci 2021 Dec 9;2:100022. Epub 2021 Feb 9.

Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali 3814, Bangladesh.

Coronavirus disease-2019 (COVID-19) is a recent world pandemic disease that is caused by a newly discovered strain of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS- CoV-2). Patients with comorbidities are most vulnerable to this disease. Therefore, cancer patients are reported to be more susceptible to COVID-19 infection, particularly lung cancer patients. To evaluate the probable reasons behind the excessive susceptibility and fatality of lung cancer patients to COVID-19 infection, we targeted the two most crucial agents, Angiotensin-converting enzyme 2 (ACE2) and C-X-C motif 10 (CXCL10). ACE2 is a receptor protein that plays a vital role in the entry of SARS-CoV-2 into the host cell and CXCL10 is a cytokine mainly responsible for the lung cell damage involving in a cytokine storm. By using the UALCAN and GEPIA2 databases, we observed that ACE2 and CXCL10 are mostly overexpressed in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). We then identified the functional significance of ACE2 and CXCL10 in lung cancer development by determining the genetic alteration frequency in their amino acid sequences using the cBioPortal web portal. Lastly, we did the pathological assessment of targeted genes using the PANTHER database. Here, we found that ACE2 and CXCL10 along with their commonly co-expressed genes are involved respectively in the binding activity and immune responses in case of lung cancer and COVID-19 infection. Finally, based on this systemic analysis, we concluded that ACE2 and CXCL10 are two possible biomarkers responsible for the higher susceptibility and fatality of lung cancer patients towards the COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.crmicr.2021.100022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871107PMC
December 2021

Recognition of plausible therapeutic agents to combat COVID-19: An omics data based combined approach.

Gene 2021 Mar 17;771:145368. Epub 2020 Dec 17.

Molecular Biotechnology Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka 1349, Bangladesh. Electronic address:

Coronavirus disease-2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has become an immense threat to global public health. In this study, we performed complete genome sequencing of a SARS-CoV-2 isolate. More than 67,000 genome sequences were further inspected from Global Initiative on Sharing All Influenza Data (GISAID). Using several in silico techniques, we proposed prospective therapeutics against this virus. Through meticulous analysis, several conserved and therapeutically suitable regions of SARS-CoV-2 such as RNA-dependent RNA polymerase (RdRp), Spike (S) and Membrane glycoprotein (M) coding genes were selected. Both S and M were chosen for the development of a chimeric vaccine that can generate memory B and T cells. siRNAs were also designed for S and M gene silencing. Moreover, six new drug candidates were suggested that might inhibit the activity of RdRp. Since SARS-CoV-2 and SARS-CoV-1 have 82.30% sequence identity, a Gene Expression Omnibus (GEO) dataset of Severe Acute Respiratory Syndrome (SARS) patients were analyzed. In this analysis, 13 immunoregulatory genes were found that can be used to develop type 1 interferon (IFN) based therapy. The proposed vaccine, siRNAs, drugs and IFN based analysis of this study will accelerate the development of new treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2020.145368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833977PMC
March 2021

Molecular characterization and functional annotation of a hypothetical protein (SCO0618) of Streptomyces coelicolor A3(2).

Genomics Inform 2020 Sep 21;18(3):e28. Epub 2020 Sep 21.

Bioinformatics Division, National Institute of Biotechnology, Savar, Dhaka 1349, Bangladesh.

Streptomyces coelicolor is a gram-positive soil bacterium which is well known for the production of several antibiotics used in various biotechnological applications. But numerous proteins from its genome are considered hypothetical proteins. Therefore, the present study aimed to reveal the functions of a hypothetical protein from the genome of S. coelicolor. Several bioinformatics tools were employed to predict the structure and function of this protein. Sequence similarity was searched through the available bioinformatics databases to find out the homologous protein. The secondary and tertiary structure were predicted and further validated with quality assessment tools. Furthermore, the active site and the interacting proteins were also explored with the utilization of CASTp and STRING server. The hypothetical protein showed the important biological activity having with two functional domain including POD-like_MBL-fold and rhodanese homology domain. The functional annotation exposed that the selected hypothetical protein could show the hydrolase activity. Furthermore, protein-protein interactions of selected hypothetical protein revealed several functional partners those have the significant role for the bacterial survival. At last, the current study depicts that the annotated hypothetical protein is linked with hydrolase activity which might be of great interest to the further research in bacterial genetics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5808/GI.2020.18.3.e28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560446PMC
September 2020

Coding-Complete Genome Sequence of SARS-CoV-2 Isolate from Bangladesh by Sanger Sequencing.

Microbiol Resour Announc 2020 Jul 9;9(28). Epub 2020 Jul 9.

Molecular Biotechnology Division, National Institute of Biotechnology, Dhaka, Bangladesh

A coding-complete genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolate was revealed. The sample for the virus was isolated from a female patient from Dhaka, Bangladesh, suffering from coronavirus disease-2019 (COVID-19).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/MRA.00626-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348026PMC
July 2020

Insight of druggable cannabinoids against estrogen receptor β in breast cancer.

J Biomol Struct Dyn 2021 Mar 11;39(5):1688-1697. Epub 2020 Mar 11.

Department of Biochemistry and Microbiology, North South University, Bashundhara, Dhaka, Bangladesh.

Breast cancer (BC) is the second most prevalent cancer worldwide. Estrogen receptor beta (ERβ) is an essential protein of breast cells to suppress estrogen-induced uncontrolled proliferation. Thus, small molecules that can modulate and enhance ERβ expression would be an effective agent to suppress BC development. Studies showed that cannabinoid (CB), specifically delta-9-tetrahydrocannabinol (Del9THC), can increase the expression of ERβ and inhibits BC cell proliferation. In this study, less psychoactive and structurally similar analogs of Del9THC were chosen as drug candidates and ERβ was targeted as a therapeutic receptor. Delta-8-tetrahydrocannabinol (Del8THC) and delta-4-isotetrahydrocannabinol (Del4isoTHC) were the drug candidates selected on the basis of literature reports, absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, medicinal chemistry profile, and physicochemical features. Molecular docking simulations were carried out to determine ligand receptor interactions and binding affinity based on free binding energy. To get a better drug, the structural modification was done on Del8THC and generated a new CB analog called Cannabinoid A. Finally, molecular interaction analysis revealed that two CBs and one of their analog interact with the active site residues of ERβ. Therefore, this study revealed a new way to discover novel drug(s) for BC patients.Communicated by Ramaswamy H. Sarma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2020.1737233DOI Listing
March 2021

Association of polymorphism in heat shock protein 70 genes with type 2 diabetes in Bangladeshi population.

Mol Genet Genomic Med 2020 02 9;8(2):e1073. Epub 2019 Dec 9.

Molecular Biotechnology Division, National Institute of Biotechnology, Dhaka, Bangladesh.

Background: Type 2 diabetes mellitus (T2DM) is a chronic disorder of which stress is a major contributor. Under stressful condition, body synthesizes a family of molecular chaperone called Heat-shock proteins (HSPs). Current study assessed the frequency and association of HSP70-hom + 2,437 T/C polymorphism with T2DM risk among Bangladeshis.

Methods: This polymorphism was selected through bioinformatics analyses and identified by PCR-RFLP method.

Results: Bioinformatics analysis identified this SNP as missense mutation which could destabilize the final HSP product. Heterozygous mutant (CT) genotype was significantly associated with T2DM incidence among the studied populations (p = .015). Further analysis revealed a strong association with female patients (p = .002), while the male group showed no association (p = .958). Moreover, the C allele was significantly associated among all diabetic patients (p = .016) and particularly in the female patient group (p = .001). However, under stressful condition, males with CT genotype were at high risk for T2DM incidence whereas, females with CT genotype showed no significant association.

Conclusions: HSP70-hom + 2,437 T/C polymorphism was found to be significantly associated with T2DM incidence in the Bangladeshi population in both stress-dependent and independent manners.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mgg3.1073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005638PMC
February 2020

An Immunopharmacoinformatics Approach in Development of Vaccine and Drug Candidates for West Nile Virus.

Front Chem 2018 6;6:246. Epub 2018 Jul 6.

Molecular Biotechnology Division, National Institute of Biotechnology, Dhaka, Bangladesh.

An outbreak of West Nile Virus (WNV) like the recent Ebola can be more epidemic and fatal to public health throughout the world. WNV possesses utmost threat as no vaccine or drug is currently available for its treatment except mosquito control. The current study applied the combined approach of immunoinformatics and pharmacoinformatics to design potential epitope-based vaccines and drug candidates against WNV. By analyzing the whole proteome of 2994 proteins, the WNV envelope glycoprotein was selected as a therapeutic target based on its highest antigenicity. After proper assessment "KSFLVHREW" and "ITPSAPSYT" were found to be the most potential T and B-cell epitopes, respectively. Besides, we have designed and validated four novel drugs from a known WNV inhibitor, AP30451 by adopting computational approaches. Toxicity assessment and drug score confirmed the effectiveness of these drug candidates. This research might greatly facilitate the wet lab experiments to develop vaccine and drug against WNV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fchem.2018.00246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043868PMC
July 2018

Pathway based therapeutic targets identification and development of an interactive database CampyNIBase of Campylobacter jejuni RM1221 through non-redundant protein dataset.

PLoS One 2018 8;13(6):e0198170. Epub 2018 Jun 8.

Molecular Biotechnology Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka, Bangladesh.

The bacterial species Campylobacter jejuni RM1221 (CjR) is the primary cause of campylobacteriosis which poses a global threat for human health. Over the years the efficacy of antibiotic treatment is becoming more fruitless due to the development of multiple drug resistant strains. Therefore, identification of new drug targets is a valuable tool for the development of new treatments for affected patients and can be obtained by targeting essential protein(s) of CjR. We conducted this in silico study in order to identify therapeutic targets by subtractive CjR proteome analysis. The most important proteins of the CjR proteome, which includes chokepoint enzymes, plasmid, virulence and antibiotic resistant proteins were annotated and subjected to subtractive analyses to filter out the CjR essential proteins from duplicate or human homologous proteins. Through the subtractive and characterization analysis we have identified 38 eligible therapeutic targets including 1 potential vaccine target. Also, 12 potential targets were found in interactive network, 5 targets to be dealt with FDA approved drugs and one pathway as potential pathway based drug target. In addition, a comprehensive database 'CampyNIBase' has also been developed. Besides the results of this study, the database is enriched with other information such as 3D models of the identified targets, experimental structures and Expressed Sequence Tag (EST) sequences. This study, including the database might be exploited for future research and the identification of effective therapeutics against campylobacteriosis. URL: (http://nib.portal.gov.bd/site/page/4516e965-8935-4129-8c3f-df95e754c562#Banner).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198170PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993290PMC
January 2019

Design of peptide-based epitope vaccine and further binding site scrutiny led to groundswell in drug discovery against Lassa virus.

3 Biotech 2018 Feb 16;8(2):81. Epub 2018 Jan 16.

2Department of Biotechnology and Genetic Engineering, Life Science Faculty, Mawlana Bhashani Science and Technology University, Santosh, Tangail, 1902 Bangladesh.

Lassa virus (LASV) is responsible for an acute viral hemorrhagic fever known as Lassa fever. Sequence analyses of LASV proteome identified the most immunogenic protein that led to predict both T-cell and B-cell epitopes and further target and binding site depiction could allow novel drug findings for drug discovery field against this virus. To induce both humoral and cell-mediated immunity peptide sequence SSNLYKGVY, conserved region 41-49 amino acids were found as the most potential B-cell and T-cell epitopes, respectively. The peptide sequence might intermingle with 17 HLA-I and 16 HLA-II molecules, also cover 49.15-96.82% population coverage within the common people of different countries where Lassa virus is endemic. To ensure the binding affinity to both HLA-I and HLA-II molecules were employed in docking simulation with suggested epitope sequence. Further the predicted 3D structure of the most immunogenic protein was analyzed to reveal out the binding site for the drug design against Lassa Virus. Herein, sequence analyses of proteome identified the most immunogenic protein that led to predict both T-cell and B-cell epitopes and further target and binding site depiction could allow novel drug findings for drug discovery field against this virus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13205-018-1106-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796937PMC
February 2018

Finding Potential Therapeutic Targets against through Proteome Exploration.

Front Microbiol 2016 22;7:1817. Epub 2016 Nov 22.

Molecular Biotechnology Division, National Institute of Biotechnology Savar, Bangladesh.

is a gram negative bacteria that causes the infectious disease "shigellosis." is responsible for developing diarrhea, fever, and stomach cramps in human. Antibiotics are mostly given to patients infected with shigella. Resistance to antibiotics can hinder its treatment significantly. Upon identification of essential therapeutic targets, vaccine and drug could be effective therapy for the treatment of shigellosis. The study was designed for the identification and qualitative characterization for potential drug targets from by using the subtractive proteome analysis. A set of computational tools were used to identify essential proteins those are required for the survival of . Total proteome (13,503 proteins) of was retrieved from NCBI and further analyzed by subtractive channel analysis. After identification of the metabolic proteins we have also performed its qualitative characterization to pave the way for the identification of promising drug targets. Subtractive analysis revealed that a list of 53 targets of were human non-homologous essential metabolic proteins that might be used for potential drug targets. We have also found that 11 drug targets are involved in unique pathway. Most of these proteins are cytoplasmic, can be used as broad spectrum drug targets, can interact with other proteins and show the druggable properties. The functionality and drug binding site analysis suggest a promising effective way to design the new drugs against . Among the 53 therapeutic targets identified through this study, 13 were found highly potential as drug targets based on their physicochemical properties whilst only one was found as vaccine target against . The outcome might also be used as module as well as circuit design in systems biology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2016.01817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118456PMC
November 2016

Identification of potential inhibitor and enzyme-inhibitor complex on trypanothione reductase to control Chagas disease.

Comput Biol Chem 2016 Dec 7;65:29-36. Epub 2016 Oct 7.

Department of Biotechnology and Genetic Engineering, Faculty of Life Scisence, Mawlana Bhashani Science and Technology University, Santosh, Tangail, Bangladesh. Electronic address:

Chagas is a parasitic disease with major threat to public health due to its resistance against commonly available drugs. Trypanothione reductase (TryR) is the key enzyme to develop this disease. Though this enzyme is well thought-out as potential drug target, the accurate structure of enzyme-inhibitor complex is required to design a potential inhibitor which is less available for TryR. In this research, we aimed to investigate the advanced drug over the available existing drugs by designing inhibitors as well as to identify a new enzyme-inhibitor complex that may act as a template for drug design. A set of analogues were designed from a known inhibitor Quinacrine Mustard (QUM) to identify the effective inhibitor against this enzyme. Further, the pharmacoinformatics elucidation and structural properties of designed inhibitor proposed effective drug candidates against Chagas disease. Molecular docking study suggests that a designed inhibitor has higher binding affinity in both crystal and modeled TryR and also poses similar interacting residues as of crystal TryR-QUM complex structure. The comparative studies based on in silico prediction proposed an enzyme-inhibitor complex which could be effective to control the disease activity. So our in silico analysis based on TryR built model, Pharmacophore and docking analysis might play an important role for the development of novel therapy for Chagas disease. But both animal model experiments and clinical trials must be done to confirm the efficacy of the therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.compbiolchem.2016.10.002DOI Listing
December 2016

Therapeutics Insight with Inclusive Immunopharmacology Explication of Human Rotavirus A for the Treatment of Diarrhea.

Front Pharmacol 2016 23;7:153. Epub 2016 Jun 23.

Molecular Biotechnology Division, National Institute of Biotechnology Dhaka, Bangladesh.

Rotavirus is the most common cause of severe infant and childhood diarrhea worldwide, and the morbidity and mortality rate is going to be outnumbered in developing countries like Bangladesh. To mitigate this substantial burden of disease, new therapeutics such as vaccine and drug are swiftly required against rotavirus. The present therapeutics insight study was performed with comprehensive immunoinformatics and pharmacoinformatics approach. T and B-cell epitopes were assessed in the conserved region of outer capsid protein VP4 among the highly reviewed strains from different countries including Bangladesh. The results suggest that epitope SU1 (TLKNLNDNY) could be an ideal candidate among the predicted five epitopes for both T and B-cell epitopes for the development of universal vaccine against rotavirus. This research also suggests five novel drug compounds from medicinal plant Rhizophora mucronata Lamk. for better therapeutics strategies against rotavirus diarrhea based on 3D structure building, pharmacophore, ADMET, and QSAR properties. The exact mode of action between drug compounds and target protein VP4 were revealed by molecular docking analysis. Drug likeness and oral bioavailability further confirmed the effectiveness of the proposed drugs against rotavirus diarrhea. This study might be implemented for experimental validation to facilitate the novel vaccine and drug design.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2016.00153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917548PMC
July 2016

Towards finding the linkage between metabolic and age-related disorders using semantic gene data network analysis.

Bioinformation 2016 31;12(1):22-7. Epub 2016 Jan 31.

Molecular Biotechnology Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka 1349, Bangladesh.

A metabolic disorder (MD) occurs when the metabolic process is disturbed. This process is carried out by thousands of enzymes participating in numerous inter-dependent metabolic pathways. Critical biochemical reactions that involve the processing and transportation of carbohydrates, proteins and lipids are affected in metabolic diseases. Therefore, it is of interest to identify the common pathways of metabolic disorders by building protein-protein interactions (PPI) for network analysis. The molecular network linkages between MD and age related diseases (ARD) are intriguing. Hence, we created networks of protein-protein interactions that are related with MD and ARD using relevant known data in the public domain. The network analysis identified known MD associated proteins and predicted genes and or its products of ARD in common pathways. The genes in the common pathways were isolated from the network and further analyzed for their co-localization and shared domains. Thus, a model hypothesis is proposed using interaction networks that are linked between MD and ARD. This data even if less conclusive finds application in understanding the molecular mechanism of known diseases in relation to observed molecular events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6026/97320630012022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857462PMC
May 2016

Treating Diabetes Mellitus: Pharmacophore Based Designing of Potential Drugs from Gymnema sylvestre against Insulin Receptor Protein.

Biomed Res Int 2016 28;2016:3187647. Epub 2016 Feb 28.

National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka 1349, Bangladesh; Molecular Biotechnology Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka 1349, Bangladesh.

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders which can affect the quality of life severely. Injectable insulin is currently being used to treat DM which is mainly associated with patient inconvenience. Small molecules that can act as insulin receptor (IR) agonist would be better alternatives to insulin injection. Herein, ten bioactive small compounds derived from Gymnema sylvestre (G. sylvestre) were chosen to determine their IR binding affinity and ADMET properties using a combined approach of molecular docking study and computational pharmacokinetic elucidation. Designing structural analogues were also performed for the compounds associated with toxicity and less IR affinity. Among the ten parent compounds, six were found to have significant pharmacokinetic properties with considerable binding affinity towards IR while four compounds were associated with toxicity and less IR affinity. Among the forty structural analogues, four compounds demonstrated considerably increased binding affinity towards IR and less toxicity compared with parent compounds. Finally, molecular interaction analysis revealed that six parent compounds and four analogues interact with the active site amino acids of IR. So this study would be a way to identify new therapeutics and alternatives to insulin for diabetic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2016/3187647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806669PMC
December 2016

Novel insights on ENTH domain-containing proteins in apicomplexan parasites.

Parasitol Res 2016 Jun 27;115(6):2191-202. Epub 2016 Feb 27.

Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Santosh, Tangail, 1902, Bangladesh.

The phylum Apicomplexa includes a large group of early branching eukaryotes having significant medical and economical importance. The molecular machinery responsible for protein trafficking is poorly understood in these apicomplexans. One of the most important proteins involved in clathrin-mediated protein trafficking is Epsin, which contains ENTH domain, a conserved domain crucial for membrane bending leading to vesicle formation. We undertook homology searching and phylogenetic analyses to produce a rigorously annotated set of Epsin homologs retrieved from diverse apicomplexan genomes. Genomic and phylogenetic comparisons revealed that apicomplexans contain unusual Epsin homologs that are distinct from those observed in mammals and yeast. Although there are four Epsin genes in mammalian system and five in the yeast genome, apicomplexan parasites consist only a single Epsin gene. The apicomplexan Epsin contains the conserved ENTH domain consisting of phosphoinositide (PtdIns)-binding sites which indicate about their functional significance in the formation of vesicles; however, the absence of ubiquitin-interacting motif (UIM) suggests a possible different mechanism for protein trafficking. The existence of dileucine motif in Plasmodium, Cryptosporidum parvum and Eimeria tenella Epsins might solve their functionality while lacking a lot of conserved motifs as this motif is known to interact with different adaptor protein complexes (AP1, AP2 and AP3). Other Epsin homologs are also shown to have different peptide motifs reported for possible interaction with α-ear appendage, γ-ear appendage and EH domain present in different adaptors. Bioinformatic and phylogenetic analyses suggest that the apicomplexan Epsins have unusual functionality from that of the mammalian Epsins. This detailed study may greatly facilitate future molecular cell biological investigation for the role of Epsins in these parasites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00436-016-4961-1DOI Listing
June 2016

Molecular Characterization of Legionellosis Drug Target Candidate Enzyme Phosphoglucosamine Mutase from Legionella pneumophila (strain Paris): An In Silico Approach.

Genomics Inform 2014 Dec 31;12(4):268-75. Epub 2014 Dec 31.

Biotechnology and Genetic Engineering Discipline, Khulna University, Khulna 9208, Bangladesh.

The harshness of legionellosis differs from mild Pontiac fever to potentially fatal Legionnaire's disease. The increasing development of drug resistance against legionellosis has led to explore new novel drug targets. It has been found that phosphoglucosamine mutase, phosphomannomutase, and phosphoglyceromutase enzymes can be used as the most probable therapeutic drug targets through extensive data mining. Phosphoglucosamine mutase is involved in amino sugar and nucleotide sugar metabolism. The purpose of this study was to predict the potential target of that specific drug. For this, the 3D structure of phosphoglucosamine mutase of Legionella pneumophila (strain Paris) was determined by means of homology modeling through Phyre2 and refined by ModRefiner. Then, the designed model was evaluated with a structure validation program, for instance, PROCHECK, ERRAT, Verify3D, and QMEAN, for further structural analysis. Secondary structural features were determined through self-optimized prediction method with alignment (SOPMA) and interacting networks by STRING. Consequently, we performed molecular docking studies. The analytical result of PROCHECK showed that 95.0% of the residues are in the most favored region, 4.50% are in the additional allowed region and 0.50% are in the generously allowed region of the Ramachandran plot. Verify3D graph value indicates a score of 0.71 and 89.791, 1.11 for ERRAT and QMEAN respectively. Arg419, Thr414, Ser412, and Thr9 were found to dock the substrate for the most favorable binding of S-mercaptocysteine. However, these findings from this current study will pave the way for further extensive investigation of this enzyme in wet lab experiments and in that way assist drug design against legionellosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5808/GI.2014.12.4.268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330265PMC
December 2014

A comprehensive immunoinformatics and target site study revealed the corner-stone toward Chikungunya virus treatment.

Mol Immunol 2015 May 14;65(1):189-204. Epub 2015 Feb 14.

Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Santosh, Tangail-1902, Bangladesh.

Recent concerning facts of Chikungunya virus (CHIKV); a Togaviridae family alphavirus has proved this as a worldwide emerging threat which causes Chikungunya fever and devitalizing arthritis. Despite severe outbreaks and lack of antiviral drug, a mere progress has been made regarding to an epitope-based vaccine designed for CHIKV. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites by using various immunoinformatics and docking simulation tools. Initially, whole proteome of CHIKV was retrieved from database and perused to identify the most immunogenic protein. Structural properties of the selected protein were analyzed. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell were checked for the selected protein. The peptide region spanning 9 amino acids from 397 to 405 and the sequence YYYELYPTM were found as the most potential B cell and T cell epitopes respectively. This peptide could interact with as many as 19 HLAs and showed high population coverage ranging from 69.50% to 84.94%. By using in silico docking techniques the epitope was further assessed for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post therapeutic strategy, three dimensional structure was predicted along with validation and verification that resulted in molecular docking study to identify the potential drug binding sites and suitable therapeutic inhibitor against targeted protein. Finally, pharmacophore study was also performed in quest of seeing potent drug activity. However, this computational epitope-based peptide vaccine designing and target site prediction against CHIKV opens up a new horizon which may be the prospective way in Chikungunya virus research; the results require validation by in vitro and in vivo experiments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molimm.2014.12.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172456PMC
May 2015

Identification of highly conserved regions in L-segment of Crimean-Congo hemorrhagic fever virus and immunoinformatic prediction about potential novel vaccine.

Adv Appl Bioinform Chem 2015 8;8:1-10. Epub 2015 Jan 8.

Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna, Bangladesh.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic viral disease with a disease fatality rate between 15% and 70%. Despite the wide range of distribution, the virus (CCHFV) is basically endemic in Africa, Asia, eastern Europe, and the Middle East. Acute febrile illness associated with petechiae, disseminated intravascular coagulation, and multiple-organ failure are the main symptoms of the disease. With all these fatal effects, CCHFV is considered a huge threat as no successful therapeutic approach is currently available for the treatment of this disease. In the present study, we have used the immunoinformatics approach to design a potential epitope-based vaccine against the RNA-dependent RNA polymerase-L of CCHFV. Both the T-cell and B-cell epitopes were assessed, and the epitope "DCSSTPPDR" was found to be the most potential one, with 100% conservancy among all the strains of CCHFV. The epitope was also found to interact with both type I and II major histocompatibility complex molecules and is considered nonallergenic as well. In vivo study of our proposed peptide is advised for novel universal vaccine production, which might be an effective path to prevent CCHF disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/AABC.S75250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4293217PMC
January 2015

A Hypothetical Protein of Alteromonas macleodii AltDE1 (amad1_06475) Predicted to be a Cold-Shock Protein with RNA Chaperone Activity.

Gene Regul Syst Bio 2014 18;8:141-7. Epub 2014 Dec 18.

Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna, Bangladesh.

Alteromonas macleodii AltDE1 is a deep sea protobacteria that is distinct from the surface isolates of the same species. This study was designed to elucidate the biological function of amad1_06475, a hypothetical protein of A. macleodii AltDE1. The 70 residues protein sequence showed considerable homology with cold-shock proteins (CSPs) and RNA chaperones from different organisms. Multiple sequence alignment further supported the presence of conserved csp domain on the protein sequence. The three-dimensional structure of the protein was also determined, and verified by PROCHECK, Verify3D, and QMEAN programs. The predicted structure contained five anti-parallel β-strands and RNA-binding motifs, which are characteristic features of prokaryotic CSPs. Finally, the binding of a thymidine-rich oligonucleotide and a single uracil molecule in the active site of the protein further strengthens our prediction about the function of amad1_06475 as a CSP and thereby acting as a RNA chaperone. The binding was performed by molecular docking tools and was compared with similar binding of 3PF5 (PDB) and 2HAX (PDB), major CSPs of Bacillus subtilis and Bacillus caldolyticus, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4137/GRSB.S20802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271719PMC
January 2015