Publications by authors named "Shama Parveen"

55 Publications

Role of "dual-personality" fragments in HEV adaptation-analysis of Y-domain region.

J Genet Eng Biotechnol 2021 Oct 12;19(1):154. Epub 2021 Oct 12.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.

Background: Hepatitis E is a liver disease caused by the pathogen hepatitis E virus (HEV). The largest polyprotein open reading frame 1 (ORF1) contains a nonstructural Y-domain region (YDR) whose activity in HEV adaptation remains uncharted. The specific role of disordered regions in several nonstructural proteins has been demonstrated to participate in the multiplication and multiple regulatory functions of the viruses. Thus, intrinsic disorder of YDR including its structural and functional annotation was comprehensively studied by exploiting computational methodologies to delineate its role in viral adaptation.

Results: Based on our findings, it was evident that YDR contains significantly higher levels of ordered regions with less prevalence of disordered residues. Sequence-based analysis of YDR revealed it as a "dual personality" (DP) protein due to the presence of both structured and unstructured (intrinsically disordered) regions. The evolution of YDR was shaped by pressures that lead towards predominance of both disordered and regularly folded amino acids (Ala, Arg, Gly, Ile, Leu, Phe, Pro, Ser, Tyr, Val). Additionally, the predominance of characteristic DP residues (Thr, Arg, Gly, and Pro) further showed the order as well as disorder characteristic possessed by YDR. The intrinsic disorder propensity analysis of YDR revealed it as a moderately disordered protein. All the YDR sequences consisted of molecular recognition features (MoRFs), i.e., intrinsic disorder-based protein-protein interaction (PPI) sites, in addition to several nucleotide-binding sites. Thus, the presence of molecular recognition (PPI, RNA binding, and DNA binding) signifies the YDR's interaction with specific partners, host membranes leading to further viral infection. The presence of various disordered-based phosphorylation sites further signifies the role of YDR in various biological processes. Furthermore, functional annotation of YDR revealed it as a multifunctional-associated protein, due to its susceptibility in binding to a wide range of ligands and involvement in various catalytic activities.

Conclusions: As DP are targets for regulation, thus, YDR contributes to cellular signaling processes through PPIs. As YDR is incompletely understood, therefore, our data on disorder-based function could help in better understanding its associated functions. Collectively, our novel data from this comprehensive investigation is the first attempt to delineate YDR role in the regulation and pathogenesis of HEV.
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http://dx.doi.org/10.1186/s43141-021-00238-8DOI Listing
October 2021

Structural exploration of Y-domain reveals its essentiality in HEV pathogenesis.

Protein Expr Purif 2021 Nov 24;187:105947. Epub 2021 Jul 24.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India. Electronic address:

Hepatitis E virus (HEV) is a major causative agent of hepatitis E infections across the globe. Although the essentiality of HEV nonstructural polyprotein (pORF1) putative Y-domain (Yd) has been established in viral pathogenesis, its structural-functional role remains elusive. The current research discusses the novel exploration on Yd protein expression, purification, biophysical characterization and structure-based docking analysis. The codon optimized synthetic gene and optimized expression parameters i.e., 5 h induction with 0.25 mM IPTG at 37 °C, resulted in efficient production of Yd protein (~40 kDa) in E. coli BL21(DE3) cells. Majority of the recombinant Yd (rYd) protein expressed as inclusion bodies was solubilized in 0.5% N-lauroylsarcosine and purified using Ni-NTA chromatography. Circular dichroism (CD) and UV visible absorption spectroscopic studies on Yd revealed both secondary and tertiary structure stability in alkaline range (pH 8.0-10.0), suggesting correlation with its physiological activity. Thus, loss in structure at low pH perhaps play crucial role in cytoplasmic-membrane interaction. The biophysical data were in good agreement with insilico structural analyses, which suggested mixed α/β fold, non-random and basic nature of Yd protein. Furthermore, due to Yd protein essentiality in HEV replication and pathogenesis, it was considered as a template for docking and drug-likeness analyses. The 3D modeling of Yd protein and structure-based screening and drug-likeness of inhibitory compounds, including established antiviral drugs led to the identification of top nine promising candidates. Nonetheless, in vitro studies on the predicted interaction of Yd with intracellular-membrane towards establishing replication-complexes as well as validations of the proposed therapeutic agents are warranted.
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http://dx.doi.org/10.1016/j.pep.2021.105947DOI Listing
November 2021

Developing Super-Hydrophobic and Abrasion-Resistant Wool Fabrics Using Low-Pressure Hexafluoroethane Plasma Treatment.

Materials (Basel) 2021 Jun 11;14(12). Epub 2021 Jun 11.

Technical Textiles Research Centre, Department of Fashion and Textiles, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK.

The growing interest in wool fibres as an eco-friendly and sustainable material for diverse industrial applications requires an enhancement of their functional performance. To address this, wool fabrics were treated in the present research with low-pressure hexafluoroethane (CF) plasma to impart superhydrophobicity and improve their abrasion resistance. Unscoured and scoured wool fabrics were treated with CF while varying plasma power (80 W and 150 W), gas flow rate (12 sccm and 50 sccm) and treatment time (6 min and 20 min), and the effect of plasma parameters on the abrasion resistance, water contact angle and dyeing behaviour of the wool fabrics was studied. Martindale abrasion testing showed that the surface abrasion of the wool fabrics increased with the number of abrasion cycles, and the samples treated with 150 W, 20 min, 12 sccm showed superior abrasion resistance. The scoured wool fabrics showed a contact angle of ~124°, which was stable for only 4 min 40 s, whereas the plasma-treated samples showed a stable contact angle of over 150°, exhibiting a stable superhydrophobic behaviour. The CF plasma treatment also significantly reduced the exhaustion of an acid dye by wool fabrics. The EDX study confirmed the deposition of fluorine-containing elements on the wool fabrics significantly altering their properties.
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http://dx.doi.org/10.3390/ma14123228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230622PMC
June 2021

Structural Characterization and Binding Studies of the Ectodomain G Protein of Respiratory Syncytial Virus Reveal the Crucial Role of pH with Possible Implications in Host-Pathogen Interactions.

ACS Omega 2021 Apr 7;6(15):10403-10414. Epub 2021 Apr 7.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India.

Respiratory syncytial virus (RSV) is a leading viral pathogen causing acute lower respiratory tract infection in children. The G protein of RSV is involved in attachment with the host cell. It is a neutralizing antigen and thus a vaccine candidate. Heparan sulfate is a type of glycosaminoglycan (GAG) present on the host cell membrane that is involved in attachment with the G protein of RSV. We describe a novel approach for efficient expression and purification of the ectodomain G protein in the prokaryotic system and its biophysical characterization. The native ectodomain G protein was purified using a two-step process by Ni-NTA and DEAE weak anion-exchange chromatography through the supernatant obtained after cell lysis. In addition, the denatured form of the protein was also purified from the solubilized inclusion bodies (IBs) by Ni-NTA affinity chromatography with a higher yield. Dynamic light scattering (DLS) was performed to confirm the homogeneity of the purified protein. The effect of pH on the stability and structure of the purified protein was studied by circular dichroism (CD), fluorescence, and absorbance spectroscopy techniques. Isothermal titration calorimetry (ITC) and microscale thermophoresis (MST) were exploited to demonstrate the interaction of heparan sulfate with the ectodomain G protein. The dynamic light scattering results showed that the purified protein was homogenic and had a well-folded native conformation. Biophysical characterization of the protein revealed that it was stable and had intact secondary and tertiary structures at pH 7.5. CD analysis revealed that the protein showed a loss in the secondary structure at pH values 5.5 and 3.5, while absorbance spectroscopy suggested a stable tertiary structure at pH values 7.5 and 5.5 with a probable aggregation pattern at pH 3.5. This loss in the structure of the ectodomain G protein at low pH can be correlated with its physiological activity. A slight change in pH might play a crucial role in host-pathogen interactions. The fluorescence intensity of the protein decreased on moving toward a lower pH with no spectral shift in emission maxima. In addition, isothermal titration calorimetry and microscale thermophoresis results showed strong binding affinity of the ectodomain G protein with heparan sulfate. The binding of heparan sulfate with protein was probably due to the electrostatic interaction of positively charged amino acid residues of the heparin-binding domain of the protein and the negatively charged group of GAGs. Future studies may involve the development of possible therapeutic agents interacting with the G protein and affecting the overall charge and pH that might hinder the host-pathogen interaction.
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http://dx.doi.org/10.1021/acsomega.1c00800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153753PMC
April 2021

Incidence, clinical evaluation and antimicrobial susceptibility pattern of bacteria isolated from diabetic patients.

Pak J Pharm Sci 2020 Nov;33(6(Supplementary)):2837-2846

Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, Pakistan.

Diabetes mellitus (DM) is classified as an endocrinological disorder of metabolism, which is marked by an increased rise in prevalence as well as incidence around the globe. The main aim of the study includes an assessment of the incidence, clinical profile evaluation and susceptibility pattern of bacteria against antimicrobial drugs in diabetic subjects. A total of 280 cases were included in the study of which the patients diagnosed with diabetes were assessed for their biochemical profiles as well as culture and sensitivity assays. 106 patients were diagnosed with diabetes out of 280 and were also associated with certain physiological disorders. Among these 106 patients, 103 patients showed an incidence of microbial infections. Of these patients, 63 were males, and 40 were females. Significant activities were observed against Klebsiella by tazobactam (68.8%). Sulzone (cefoperozone + sulbactam) demonstrated the most significant antimicrobial activities against Staphylococcus aureus (87.5%). Efficacy of Cefipime against Pseudomonas was quite substantial (66.6%) followed by Sulphamethazole (61.1%). Maximum activities were observed by cefixime against E. coli (61.5%) followed by nitrofurantoin (43.5%). Infections caused by Pseudomonas and Staphylococcus aureus were present in 18 and 8 patients, respectively.
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November 2020

Inhibition of Chikungunya Virus Infection by 4-Hydroxy-1-Methyl-3-(3-morpholinopropanoyl)quinoline-2(1)-one (QVIR) Targeting nsP2 and E2 Proteins.

ACS Omega 2021 Apr 31;6(14):9791-9803. Epub 2021 Mar 31.

Molecular Virology Laboratory, Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India.

The re-emergence of Chikungunya virus (CHIKV) infection in humans with no approved antiviral therapies or vaccines is one of the major problems with global significance. In the present investigation, we screened 80 in-house quinoline derivatives for their anti-CHIKV activity by computational techniques and found 4-hydroxy-1-methyl-3-(3-morpholinopropanoyl)quinoline-2(1)-one (QVIR) to have potential binding affinities with CHIKV nsP2 and E2 glycoproteins. QVIR was evaluated for its anti-CHIKV potential. QVIR showed strong inhibition of CHIKV infection with an EC (50% effective concentration) value of 2.2 ± 0.49 μM without significant cytotoxicity (CC > 200 μM) and was chosen for further elucidation of its antiviral mechanism. The infectious viral particle formation was abolished by approximately 72% at a QVIR concentration of 20 μM during infection in the BHK-21 cell line, and the CHIKV RNA synthesis was diminished by 84% for nsP2 as well as 74% for E2, whereas the levels of viral proteins were decreased by 69.9% for nsP2 and 53.9% for E2. Flow cytometry analysis confirmed a huge decline in the expression of viral nsP2 and E2 proteins by 71.84 and 67.7%, respectively. Time of addition experiments indicated that QVIR inhibited viral infection at early and late stages of viral replication cycle, and the optimal inhibition was observed at 16 h post infection. The present study advocates for the first time that QVIR acts as a substantial and potent inhibitor against CHIKV and might be as an auspicious novel drug candidate for the development of therapeutic agents against CHIKV infections.
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http://dx.doi.org/10.1021/acsomega.1c00447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047676PMC
April 2021

An Study on the Role of Hepatitis B Virus X Protein C-Terminal Truncation in Liver Disease Development.

Front Genet 2021 12;12:633341. Epub 2021 Mar 12.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.

Hepatitis B virus X protein C-terminal 127 amino acid truncation is often found expressed in hepatocellular carcinoma (HCC) tissue samples. The present study tried to determine the role of this truncation mutant in the hepatitis B-related liver diseases such as fibrosis, cirrhosis, HCC, and metastasis. HBx gene and its 127 amino acid truncation mutant were cloned in mammalian expression vectors and transfected in human hepatoma cell line. Changes in cell growth/proliferation, cell cycle phase distribution, expression of cell cycle regulatory genes, mitochondrial depolarization, and intracellular reactive oxygen species (ROS) level were analyzed. Green fluorescent protein (GFP)-tagged version of HBx and the truncation mutant were also created and the effects of truncation on HBx intracellular expression pattern and localization were studied. Effect of time lapse on protein expression pattern was also analyzed. The truncation mutant of HBx is more efficient in inducing cell proliferation, and causes more ROS production and less mitochondrial depolarization as compared with wild type (wt) HBx. In addition, gene expression is altered in favor of carcinogenesis in the presence of the truncation mutant. Furthermore, mitochondrial perinuclear aggregation is achieved earlier in the presence of the truncation mutant. Therefore, HBx C-terminal 127 amino acid truncation might be playing important roles in the development of hepatitis B-related liver diseases by inducing cell proliferation, altering gene expression, altering mitochondrial potential, inducing mitochondrial clustering and oxidative stress, and changing HBx expression pattern.
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http://dx.doi.org/10.3389/fgene.2021.633341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994528PMC
March 2021

DFT Study on the Electronic Properties, Spectroscopic Profile, and Biological Activity of 2-Amino-5-trifluoromethyl-1,3,4-thiadiazole with Anticancer Properties.

ACS Omega 2020 Nov 13;5(46):30073-30087. Epub 2020 Nov 13.

Department of Physics, University of Lucknow, Lucknow 226007, India.

Extensive investigation on the molecular and electronic structure of 2-amino-5-trifluoromethyl-1,3,4-thiadiazole in the ground state and in the first excited state has been performed. The energy barrier corresponding to the conversion between imino and amino tautomers has been calculated, which indicates the existence of amino tautomer in solid state for the title compound. The FT-Raman and FT-IR spectra were recorded and compared with theoretical vibrational wavenumbers, and a good coherence has been observed. The MESP map, dipole moment, polarizability, and hyperpolarizability have been calculated to comprehend the properties of the title molecule. High polarizability value estimation of the title compound may enhance its bioactivity. Natural bonding orbital analysis has been done on monomer and dimer to investigate the charge delocalization and strength of hydrogen bonding, respectively. Strong hydrogen bonding interaction energies of 17.09/17.49 kcal mol have been calculated at the B3LYP/M06-2X functional. The UV-vis spectrum was recorded and related to the theoretical spectrum. The title compound was biologically examined for anticancer activity by studying the cytotoxic performance against two human cancer cell lines (A549 and HeLa) along with the molecular docking simulation. Both molecular docking and cytotoxic performance against cancer cell lines show positive outcomes, and the title compound appears to be a promising anticancer agent.
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http://dx.doi.org/10.1021/acsomega.0c04474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689922PMC
November 2020

Circulation of dengue virus serotypes in hyperendemic region of New Delhi, India during 2011-2017.

J Infect Public Health 2020 Dec 2;13(12):1912-1919. Epub 2020 Nov 2.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India. Electronic address:

Background: Dengue fever has become a hampering menace in New Delhi India, since the disease has become hyperendemic, due to circulation of multiple serotypes of dengue virus (DENV). This hyperendemicity poses a greater risk of secondary infections in human health system. This is a major issue which leads to apprehension amongst the researchers and health organizations and thus requires regular epidemiological surveillance.

Methods: We analyzed the prevalence and serotypic distribution of dengue fever cases reported from the Southern part of New Delhi during continued surveillance from 2011 to 2017. The blood samples for the investigation were obtained from the patients suspected with dengue fever attending the OPD at a local Health Centre. The data for 2011-2016 was already published from our laboratory. The samples collected during 2017 were serotyped and characterized in the present study.

Results: A total of 565 samples (59%) were positive for DENV of 958 samples tested by RT-PCR during 7 years (2011-2017). Our study has shown that most infections were caused by DENV-2 during 2011-2015. The data has shown occurrence of all four serotypes of DENV during 2015 and predominance of DENV-3 in 2016 and 2017. Further, predominant combination of DENV-1 and DENV-2 was found in most of the co-infections. To the best of our knowledge this is the first study showing the epidemiological trend of dengue fever in reference to the circulating DENV serotypes and co-infections from a hyperendemic region of New Delhi during 2011-2017.

Conclusions: This hyperendemic pattern of DENV and instantaneous shift in circulation of its serotypes is likely pose a greater risk of secondary infections. Inclusion of comprehensive community and hospital surveillance of dengue fever will assist in formulation and implementation of effective control measures.
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http://dx.doi.org/10.1016/j.jiph.2020.10.009DOI Listing
December 2020

Expression of transforming growth factor beta in oral submucous fibrosis.

J Oral Biol Craniofac Res 2020 Apr-Jun;10(2):166-170. Epub 2020 Apr 13.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.

Background: Oral submucous fibrosis (OSMF) is a premalignant condition mainly caused by areca nut chewing and is characterized by progressive fibrosis of submucosal tissues and epithelial atrophy. Activation of transforming growth factor beta (TGF-β) signaling is considered main causative event for increased collagen production and fibrosis. In this study, molecular pathogenesis of OSMF was investigated based on the expression of the TGF-β genes in OSMF tissues compared to normal controls.

Methods: A total of 33 OSMF and 10 normal tissues were collected from patients and their clinic-epidemiological data was recorded. The expression of TGF-β isoform genes- TGF β1, TGF β2, TGF β3 and its receptor TGF βR1, TGF βR2 was studied by real time polymerase chain reaction (PCR). Comparison of the expression of these genes among normal controls and OSMF patients was done. The PCR results were confirmed by histopathological and immunohistochemical staining.

Results: The histological changes included atrophic epithelium, loss of rete ridges, presence of inflammatory cells and dense collagen bundles in connective tissue. PCR showed statistically significant upregulation of TGF-β isoforms in OSMF as compared to normal tissues. Of the three isoforms, maximum fold change was observed in TGF-β1. Similarly, both TGF-βR1 and TGF-βR2 were found to be elevated in OSMF tissues compared to normal. The semi-quantitative analysis by immunohistochemical staining revealed statistically significant difference between normal and OSMF tissues.

Conclusion: TGF-β signaling plays a major role in the molecular pathogenesis of OSMF as shown by increased mRNA expression of all the three TGF-β isotypes and their receptors.
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http://dx.doi.org/10.1016/j.jobcr.2020.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254463PMC
April 2020

Emergence of deadly severe acute respiratory syndrome coronavirus-2 during 2019-2020.

Virusdisease 2020 Apr 8:1-9. Epub 2020 Apr 8.

1Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025 India.

Wuhan, the city in Hubei province in China is in the focus of global community due to the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), formerly known as 2019-nCoV. The virus emerged in humans from Wuhan seafood market probably via zoonotic transmission. Within a few days the virus spread its tentacles rapidly to neighboring cities in China and to different geographical regions through travelers and to some extent by human to human transmission leading to significant disease burden globally. More than 2,00,000 people (including more than 8000 deaths) have been infected with this respiratory illness across 167 countries and territories worldwide leading to a pandemic. The present review provides an outline about emergence and spread of SARS-CoV-2 from Wuhan, China in 2019-2020. We have also provided information about the classification, genome, proteins, clinical presentation of COVID-19, type of clinical specimens to be collected and diagnostic methods adopted to identify the respiratory illness. In addition we have also provided information about transmission dynamics, prevention measures and treatment options that are available at the present. Subsequently, we have given a comprehensive overview of the spread of this infection from China to the other parts of the globe. Management of the ongoing outbreak of SARS-CoV-2 encompassing surveillance, clinical, immunological, genetic and evolutionary investigations are likely to provide the desired results. Joint efforts of global scientific community are needed at this hour in terms of enhancement of research on development of accurate diagnostics, antiviral therapeutics and finally into formation of an effective vaccine against the emerging novel coronavirus.
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http://dx.doi.org/10.1007/s13337-020-00575-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138902PMC
April 2020

Network-based identification of signature genes KLF6 and SPOCK1 associated with oral submucous fibrosis.

Mol Clin Oncol 2020 Apr 30;12(4):299-310. Epub 2020 Jan 30.

Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India.

The molecular mechanism of oral submucous fibrosis (OSF) is yet to be fully elucidated. The identification of reliable signature genes to screen patients with a high risk of OSF and to provide oral cancer surveillance is therefore required. The present study produced a filtering criterion based on network characteristics and principal component analysis, and identified the genes that were involved in OSF prognosis. Two gene expression datasets were analyzed using meta-analysis, the results of which revealed 1,176 biologically significant genes. A co-expression network was subsequently constructed and weighted gene modules were detected. The pathway and functional enrichment analyses of the present study allowed for the identification of modules 1 and 2, and their respective genes, SPARC (osteonectin), cwcv and kazal like domain proteoglycan 1 (SPOCK1) and kruppel like factor 6 (KLF6), which were involved in the occurrence of OSF. The results revealed that both genes had a prominent role in epithelial to mesenchymal transition during OSF progression. The genes identified in the present study require further exploration and validation within clinical settings to determine their roles in OSF.
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http://dx.doi.org/10.3892/mco.2020.1991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058035PMC
April 2020

Potential of nano-phytochemicals in cervical cancer therapy.

Clin Chim Acta 2020 Jun 1;505:60-72. Epub 2020 Feb 1.

Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, India. Electronic address:

Cervical cancer is common among women with a recurrence rate of 35% despite surgery, radiation, and chemotherapy. Patients receiving chemotherapy or radiotherapy routinely experience several side effects including toxicity, non-targeted damage of tissues, hair loss, neurotoxicity, multidrug resistance (MDR), nausea, anemia and neutropenia. Phytochemicals can interfere with almost every stage of carcinogenesis to prevent cancer development. Many natural compounds are known to activate/deactivate multiple redox-sensitive transcription factors that modulate tumor signaling pathways. Polyphenols have been found to be promising agents against cervical cancer. However, applications of phytochemicals as a therapeutic drug are limited due to low oral bioavailability, poor aqueous solubility and requirement of high doses. Nano-sized phytochemicals (NPCs) are promising anti-cancer agents as they are required in minute quantities which lowers overall treatment costs. Several phytochemicals, including quercetin, lycopene, leutin, curcumin, green tea polyphenols and others have been packaged as nanoparticles and proven to be useful in nano-chemoprevention and nano-chemotherapy. Nanoparticles have high biocompatibility, biodegradability and stability in biological environment. Nano-scale drug delivery systems are excellent source for enhanced drug specificity, improved absorption rates, reduced drug degradation and systemic toxicity. The present review discusses current knowledge in the involvement of phytochemical nanoparticles in cervical cancer therapy over conventional chemotherapy.
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http://dx.doi.org/10.1016/j.cca.2020.01.035DOI Listing
June 2020

Evolutionary analysis of the ON1 genotype of subtype a respiratory syncytial virus in Riyadh during 2008-16.

Infect Genet Evol 2020 04 24;79:104153. Epub 2019 Dec 24.

Protein Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia; Centre of Excellence in Biotechnology Research, Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia. Electronic address:

Respiratory syncytial virus is a leading cause of acute respiratory tract infection (ARI) in children worldwide. Limited information is available on molecular epidemiology of respiratory syncytial virus (RSV) from Saudi Arabia. An attempt was made to identify and characterize RSV strains in nasopharyngeal aspirates collected from hospitalized symptomatic ARI pediatric patients with <5 years of age from Riyadh, Saudi Arabia during 2016. All the samples (n = 100) were tested for RSV by real time PCR. The RSV strains were characterized by sequencing of the second hypervariable region of G protein gene. The study sequences along with the previously reported strains from Saudi Arabia were assessed for mutational, glycosylation, phylogenetic, selection pressure and entropy analyses. Fifty percent of the nasopharyngeal aspirates were positive for RSV. The RSVA (72%) predominated as compared to RSVB (24%) during the study. The study RSVA strains (n = 29) clustered into NA1 and ON1 genotypes whereas all the RSVB sequences (n = 5) were in BA genotype by phylogenetic analysis. Interestingly, 97% of RSVA sequences (n =28) clustered into ON1 genotype with 72 bp duplication in the G protein gene. Numerous mutations, variable N-/O-glycosylation sites and purifying selections were observed in the ON1 genotype. Positive selection with high entropy value was observed for three codons in ON1 (247, 262 and 274 amino acids) indicating higher probability of variations at these positions. Our study shows the progressive emergence and predominance of the ON1 genotype in Riyadh, Saudi Arabia during 2008-16. ON1 genotype almost replaced the previously circulating RSVA strains in this region during this period. Contribution of host genetic and immune factors towards disease severity of the ON1 genotype needs to be investigated in future studies. RSV surveillance in future elaborate investigations are needed in this region to understand its disease burden, evolutionary trajectory and circulation dynamics warranting steps towards vaccine development.
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http://dx.doi.org/10.1016/j.meegid.2019.104153DOI Listing
April 2020

Respiratory syncytial virus infections in India: Epidemiology and need for vaccine.

Indian J Med Microbiol 2018 Oct-Dec;36(4):458-464

Department of Microbiology, Dr. Baba Saheb Ambedkar Medical College and Hospital, New Delhi, India.

Respiratory syncytial virus (RSV) has been identified as a leading cause of lower respiratory tract infections in young children and elderly. It is an enveloped negative-sense RNA virus belonging to Genus Orthopneumovirus. The clinical features of RSV infection range from mild upper-respiratory-tract illnesses or otitis media to severe lower-respiratory-tract illnesses. Current estimates show that about 33.1 million episodes of RSV-acute lower respiratory infection (ALRI) occurred in young children in 2015, of these majority that is, about 30 million RSV-ALRI episodes occurred in low-middle-income countries. In India, the rates of RSV detection in various hospital- and community-based studies mostly done in children vary from 5% to 54% and from 8% to 15%, respectively. Globally, RSV epidemics start in the South moving to the North. In India, RSV mainly peaks in winter in North India and some correlation with low temperature has been observed. Different genotypes of Group A (GA2, GA5, NA1 and ON1) and Group B (GB2, SAB4 and BA) have been described from India. The burden of RSV globally has kept it a high priority for vaccine development. After nearly 50 years of attempts, there is still no licensed vaccine and challenges to obtain a safe and effective vaccine is still facing the scientific community. The data in this review have been extracted from PubMed using the keywords RSV and Epidemiology and India. The data have been synthesised by the authors.
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http://dx.doi.org/10.4103/ijmm.IJMM_19_5DOI Listing
August 2019

An overview of respiratory syncytial virus infections in Saudi Arabia.

J Infect Dev Ctries 2018 11 30;12(11):929-936. Epub 2018 Nov 30.

College of Science, King Saud University, Riyadh, Saudi Arabia.

Respiratory syncytial virus (RSV) is a major pathogen of acute respiratory tract infection (ARI) in different geographical regions including Saudi Arabia. Numerous hospital-based investigations have revealed the RSV prevalence between 0.2-54% in the paediatric population with ARI/ALRI from Saudi Arabia during 1991-2015. Maximum RSV infections occurred in children less than 1 year of age (51-97%) and male children (51-69%) were more commonly affected than females (31-49%). RSV infections are reported mostly during winter season suggesting seasonal distribution of the virus. Other respiratory viruses reported from this region are adenovirus, influenza, parainfluenza, human metapneumovirus and rhinovirus including many mixed infections. A few studies have reported the phylogenetic analysis of the circulating strains of RSV. These studies have revealed that circulating group A-RSV Saudi strains belonged to NA1 and ON1 genotypes and group B-RSV viruses clustered in the BA genotype. Molecular characterization of the Saudi strains was further carried out by mutational, selection pressure and glycosylation site analyses. We have compiled all the eighteen studies of RSV infection from Saudi Arabia in the form of this review and concluded that detailed comprehensive surveillance of RSV and other viruses in community and hospital settings is required. Information on the molecular characterization of currently circulating strains of RSV will contribute towards better understanding of the epidemiology and evolutionary dynamics of this viral pathogen. Moreover, the determination of the genetic composition of circulating RSV strains will be important during evaluation of initial vaccine trials.
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http://dx.doi.org/10.3855/jidc.10736DOI Listing
November 2018

Circulation of single serotype of Dengue Virus (DENV-3) in New Delhi, India during 2016: A change in the epidemiological trend.

J Infect Public Health 2019 Jan - Feb;12(1):49-56. Epub 2018 Sep 28.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India. Electronic address:

Background: Dengue is a rapidly emerging arthropod borne viral infection affecting tropical and sub-tropical regions of the world. Dengue is an acute febrile illness but sometimes causes more fatal complications like dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). Delhi, the capital of India has become hyper endemic for dengue virus because all the four serotypes are circulating here.

Methods: The present study describes the identification of dengue virus from clinical samples collected from the suspected dengue patients from New Delhi, India during 2016. The CprM region of Dengue virus genome was analyzed for phylogenetic, selection pressure and Shannon entropy analyses.

Results: The present study reports circulation of a single serotype (DENV-3) in New Delhi, during 2016. The phylogenetic analysis revealed that Indian subcontinent (genotype III) of DENV-3 was circulating in Delhi during this period. Neutral selection pressure in the analyzed region revealed relatively conserved nature of this part of the Dengue virus genome. Amino acid at 31 was positively selected and had high entropy value suggesting probability of variation at this position.

Conclusions: The changing trend in circulation of dengue virus serotypes necessitates the continuous epidemiological surveillance for the dengue outbreaks in this region.
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http://dx.doi.org/10.1016/j.jiph.2018.08.008DOI Listing
April 2019

A green approach of improving interface and performance of plant fibre composites using microcrystalline cellulose.

Carbohydr Polym 2018 Oct 26;197:137-146. Epub 2018 May 26.

Centre for Textile Science and Technology (2C2T), School of Engineering, University of Minho, Campus de Azurem, 4800-058 Guimaraes, Portugal.

In contrast to the conventional methods of improving interface and performances of plant fibre composites through fibre surface modification, this paper reports a novel approach based on the dispersion of microcrystalline cellulose (MCC) in the composite's matrix. MCC was dispersed within the matrix of jute fibre reinforced epoxy composites to improve the fibre/matrix interface as well as mechanical, dynamic-mechanical and thermal performances. To develop these novel jute/epoxy/MCC hierarchical composites, MCC was first dispersed within an epoxy resin using a short ultrasonication process (1 h) and subsequently, the MCC/epoxy suspensions were infused through jute fabrics using the vacuum infusion technique and cured. Hierarchical composites by dispersing multi-walled carbon nanotubes (MWCNTs) within the epoxy resin were also fabricated to compare their performance with MCC based hierarchical composites. Interface (single fibre pull-out test), mechanical (tensile, flexural, izod impact), thermal (thermogravimetric analysis) and dynamic mechanical performances of the developed composites were thoroughly studied. It was observed that the addition of MCC to the epoxy matrix led to a significant increase in the interfacial shear strength (IFSS) between jute fibres and the epoxy matrix and consequently, resulted up to 18.4%, 21.5%, 28.3%, 67% and 49.5% improvements in the tensile strength, flexural strength, impact energy, storage and loss moduli, respectively as compared to the neat jute/epoxy composites. The above improvements achieved with MCC were significantly higher as compared to the MWCNT based hierarchical composites developed using the same technique.
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http://dx.doi.org/10.1016/j.carbpol.2018.05.074DOI Listing
October 2018

Global prevalence and distribution of coinfection of malaria, dengue and chikungunya: a systematic review.

BMC Public Health 2018 06 8;18(1):710. Epub 2018 Jun 8.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.

Background: Malaria, Dengue and Chikungunya are vector borne diseases with shared endemic profiles and symptoms. Coinfections with any of these diseases could have fatal outcomes if left undiagnosed. Understanding the prevalence and distribution of coinfections is necessary to improve diagnosis and designing therapeutic interventions.

Methods: We have carried out a systematic search of the published literature based on PRISMA guidelines to identify cases of Malaria, Dengue and Chikungunya coinfections. We systematically reviewed the literature to identify eligible studies and extracted data regarding cases of coinfection from cross sectional studies, case reports, retrospective studies, prospective observational studies and surveillance reports.

Results: Care full screening resulted in 104 publications that met the eligibility criteria and reported Malaria/Dengue, Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections. These coinfections were spread over six geographical locations and 42 different countries and are reported more frequently in the last 15 years possibly due to expanding epidemiology of Dengue and Chikungunya. Few of these reports have also analysed distinguishing features of coinfections. Malaria/Dengue coinfections were the most common coinfection followed by Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections. P. falciparum and P. vivax were the commonest species found in cases of malaria coinfections and Dengue serotype-4 commonest serotype in cases of dengue coinfections. Most studies were reported from India. Nigeria and India were the only two countries from where all possible combinations of coinfections were reported.

Conclusion: We have comprehensively reviewed the literature associated with cases of coinfections of three important vector borne diseases to present a clear picture of their prevalence and distribution across the globe. The frequency of coinfections presented in the study suggests proper diagnosis, surveillance and management of cases of coinfection to avoid poor prognosis of the underlying etiology.
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http://dx.doi.org/10.1186/s12889-018-5626-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992662PMC
June 2018

BA9 lineage of respiratory syncytial virus from across the globe and its evolutionary dynamics.

PLoS One 2018 25;13(4):e0193525. Epub 2018 Apr 25.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.

Respiratory syncytial virus (RSV) is an important pathogen of global significance. The BA9 is one of the most predominant lineages of the BA genotype of group B RSV that has acquired a 60bp duplication in its G protein gene. We describe the local and global evolutionary dynamics of the second hyper variable region in the C- terminal of the G protein gene of the BA9 lineage. A total of 418 sequences (including 31 study and 387 GenBank strains) from 29 different countries were used for phylogenetic analysis. This analysis showed that the study strains clustered with BA (BA9 and BA8) and SAB4 genotype of group B RSV. We performed time-scaled evolutionary clock analyses using Bayesian Markov chain Monte Carlo methods. We also carried out glycosylation, selection pressure, mutational, entropy and Network analyses of the BA9 lineage. The time to the most recent common ancestor (tMRCA) of the BA genotype and BA9 lineage were estimated to be the years 1995 (95% HPD; 1987-1997) and 2000 (95% HPD; 1998-2001), respectively. The nucleotide substitution rate of the BA genotype [(4.58×10-3 (95% HPD; 3.89-5.29×10-3) substitution/site/year] was slightly faster than the BA9 lineage [4.03×10-3 (95% HPD; 4.65-5.2492×10-3)]. The BA9 lineage was categorized into 3 sub lineages (I, II and III) based on the Bayesian and Network analyses. The local transmission pattern suggested that BA9 is the predominant lineage of BA viruses that has been circulating in India since 2002 though showing fluctuations in its effective population size. The BA9 lineage established its global distribution with report from 23 different countries over the past 16 years. The present study augments our understanding of RSV infection, its epidemiological dynamics warranting steps towards its overall global surveillance.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193525PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919079PMC
July 2018

Global distribution of NA1 genotype of respiratory syncytial virus and its evolutionary dynamics assessed from the past 11 years.

Infect Genet Evol 2018 06 8;60:140-150. Epub 2018 Feb 8.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India. Electronic address:

Respiratory syncytial virus (RSV) is a potent pathogen having global distribution. The main purpose of this study was to gain an insight into distribution pattern of the NA1 genotype of group A RSV across the globe together with its evolutionary dynamics. We focused on the second hypervariable region of the G protein gene and used the same for Phylogenetic, Bayesian and Network analyses. Eighteen percent of the samples collected from 500 symptomatic pediatric patients with acute respiratory tract infection (ARI) were found to be positive for RSV during 2011-15 from New Delhi, India. Of these, group B RSV was predominant and clustered into two different genotypes (BA and SAB4). Similarly, group A viruses clustered into two genotypes (NA1 and ON1). The data set from the group A viruses included 543 sequences from 23 different countries including 67 strains from India. The local evolutionary dynamics suggested consistent virus population of NA1 genotype in India during 2009 to 2014. The molecular clock analysis suggested that most recent common ancestor of group A and NA1 genotype have emerged in during the years 1953 and 2000, respectively. The global evolutionary rates of group A viruses and NA1 genotype were estimated to be 3.49 × 10 (95% HPD, 2.90-4.17 × 10) and 3.56 × 10 (95% HPD, 2.91 × 10-4.18 × 10) substitution/site/year, respectively. Analysis of the NA1 genotype of group A RSV reported during 11 years i.e. from 2004 to 2014 showed its dominance in 21 different countries across the globe reflecting its evolutionary dynamics. The Network analysis showed highly intricate but an inconsistent pattern of haplotypes of NA1 genotype circulating in the world. Present study seems to be first comprehensive attempt on global distribution and evolution of NA1 genotype augmenting the optimism towards the vaccine development.
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http://dx.doi.org/10.1016/j.meegid.2018.02.010DOI Listing
June 2018

A clinical report on mixed infection of malaria, dengue and chikungunya from New Delhi, India.

Virusdisease 2017 Dec 19;28(4):422-424. Epub 2017 Oct 19.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.

Arthropod-borne infections like malaria, dengue and chikungunya fever are transmitted by mosquitoes. The present report describes an unusual case of mixed infection with malaria, dengue and chikungunya viruses in a 21 year old male patient from New Delhi, India during monsoon season of 2016. The malarial fever was diagnosed by thin slide microscopy and antigen test. Chikungunya virus IgM was detected in the sample by the card test. Dengue and chikungunya viruses were further confirmed by RT-PCR for CprM and E1 gene respectively. Phylogenetic analysis clustered the study dengue virus serotype 3 sequence in the genotype III. Thus, the mono infections can not be differentiated from concurrent infections on the basis of clinical symptoms, the appropriate laboratory diagnosis is essential for the accurate pathogen confirmation. Precise and appropriate identification of the multiple pathogens in such clinical cases will assist in the effective management of these arthropod mediated infections.
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http://dx.doi.org/10.1007/s13337-017-0404-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747841PMC
December 2017

Concurrent Infection with Plasmodium vivax and the Dengue and Chikungunya Viruses in a Paediatric Patient from New Delhi, India in 2016.

Intervirology 2017 15;60(1-2):48-52. Epub 2017 Sep 15.

Centre for Interdisciplinary Research in Basic Sciences, New Delhi, India.

Dengue and chikungunya fevers are transmitted by the common mosquito vector Aedes and malaria by Anopheles. Concurrent infections are reported due to co-circulation of these pathogens, especially in endemic regions. We report a rare case of triple infection with 3 arthropod-borne pathogens (Plasmodium vivax and the dengue and chikungunya viruses) in a 3-year-old child from New Delhi, India, in August 2016. The viruses were identified by RT-PCR and the parasite by microscopy and antigen detection. The dengue virus serotype 3 sequence was clustered in the genotype III by the phylogenetic analysis. Mixed infection with multiple pathogens is a challenge for accurate diagnosis due to the overlapping clinical symptoms. The accurate and timely diagnosis of multiple pathogens in such cases is important for rapid and effective patient management.
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http://dx.doi.org/10.1159/000479430DOI Listing
May 2018

Evolution and Emergence of Pathogenic Viruses: Past, Present, and Future.

Intervirology 2017 4;60(1-2):1-7. Epub 2017 Aug 4.

Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Incidences of emerging/re-emerging deadly viral infections have significantly affected human health despite extraordinary progress in the area of biomedical knowledge. The best examples are the recurring outbreaks of dengue and chikungunya fever in tropical and sub-tropical regions, the recent epidemic of Zika in the Americas and the Caribbean, and the SARS, MERS, and influenza A outbreaks across the globe. The established natural reservoirs of human viruses are mainly farm animals, and, to a lesser extent, wild animals and arthropods. The intricate "host-pathogen-environment" relationship remains the key to understanding the emergence/re-emergence of pathogenic viruses. High population density, rampant constructions, poor sanitation, changing climate, and the introduction of anthropophilic vectors create selective pressure on host-pathogen reservoirs. Nevertheless, the knowledge and understanding of such zoonoses and pathogen diversity in their known non-human reservoirs are very limited. Prevention of arboviral infections using vector control methods has not been very successful. Currently, new approaches to protect against food-borne infections, such as consuming only properly cooked meats and animal products, are the most effective control measures. Though significant progress in controlling human immunodeficiency virus and hepatitis viruses has been achieved, the unpredictable nature of evolving viruses and the rare occasions of outbreaks severely hamper control and preventive modalities.
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http://dx.doi.org/10.1159/000478729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179518PMC
May 2018

Ultrasensitive, highly selective, and real-time detection of protein using functionalized CNTs as MIP platform for FOSPR-based biosensor.

Nanotechnology 2017 Sep 15;28(35):355503. Epub 2017 Jun 15.

Physics Department, Indian Institute of Technology Delhi, New Delhi-110016, India.

A facile approach is presented for the detection of bovine serum albumin (BSA), based on fiber optic surface plasmon resonance (FOSPR) combined with molecular imprinting (MI). The probe is fabricated by exploiting the plasmonic property of silver thin film and vinyl-functionalised carbon nanotube-based MIP platform. BSA template molecules are imprinted on the MIP layer coated over multi-walled carbon nanotubes to ensure high specificity of the probe in the interfering environments. In addition, FOSPR endorses the sensor capability of real-time and remote sensing along with very high sensitivity due to the use of nanostructured MI platform. The response of the probe is considered in terms of the absorbance spectrum recorded for various concentrations of BSA. The sensor shows a wide dynamic range of 0-350 ng l with a considerably linear response up to 100 ng l in the peak absorbance wavelength with BSA concentration. A highest sensitivity of 0.862 nm per ng l is achieved for the lowest concentration of BSA and it decreases with the increase in BSA concentration. The performance of the present sensor is compared with those reported in the literature in terms of the limit of detection. It is found that the probe possesses a lowest LOD of 0.386 ng l in addition to other advantages such as real-time online monitoring, high sensitivity, high specificity, and remote sensing.
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http://dx.doi.org/10.1088/1361-6528/aa79e5DOI Listing
September 2017

Potential entry inhibitors of the envelope protein (E2) of Chikungunya virus: in silico structural modeling, docking and molecular dynamic studies.

Virusdisease 2017 Mar 9;28(1):39-49. Epub 2017 Feb 9.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025 India.

Chikungunya fever is an arboviral infection caused by the Chikungunya virus (CHIKV) and is transmitted by mosquito. The envelope protein (E2) of Chikungunya virus is involved in attachment of virion with the host cell. The present study was conceptualized to determine the structure of E2 protein of CHIKV and to identify the potential viral entry inhibitors. The secondary and tertiary structure of E2 protein was determined using bioinformatics tools. The mutational analysis of the E2 protein suggested that mutations may stabilize or de-stabilize the structure which may affect the structure-function relationship. In silico screening of various compounds from different databases identified two lead molecules i.e. phenothiazine and bafilomycin. Molecular docking and MD simulation studies of the E2 protein and compound complexes was carried out. This analysis revealed that bafilomycin has high docking score and thus high binding affinity with E2 protein suggesting stable protein-ligand interaction. Further, MD simulations suggested that both the compounds were stabilizing E2 protein. Thus, bafilomycin and phenothiazine may be considered as the lead compounds in terms of potential entry inhibitor for CHIKV. Further, these results should be confirmed by comprehensive cell culture, cytotoxic assays and animal experiments. Certain derivatives of phenothiazines can also be explored in future studies for entry inhibitors against CHIKV. The present investigation thus provides insight into protein structural dynamics of the envelope protein of CHIKV. In addition the study also provides information on the dynamics of interaction of E2 protein with entry inhibitors that will contribute towards structure based drug design.
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http://dx.doi.org/10.1007/s13337-016-0356-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5377863PMC
March 2017

Camelus dromedarius glucose transporter 4: in silico analysis, cloning, expression, purification and characterisation in E. coli.

Arch Physiol Biochem 2017 Oct 25;123(4):254-264. Epub 2017 Apr 25.

a Protein Research Chair, Department of Biochemistry, College of Science , King Saud University , Riyadh , Saudi Arabia.

Camels have exceptional carbohydrate metabolism as their plasma glucose level is high and have low whole body insulin sensitivity, similar to that observed in type 2 diabetes patients. We aimed at studing an important component of insulin signalling pathway, the GLUT4, in camel. Camelus dromedarius GLUT4 (CdGLUT4) CDS is 1530 nucleotide in length that encodes for a 55KDa protein. CdGLUT4 has 23 amino acid substitutions and 3N-glycosylation sites, compared to 2 in Human GLUT4. 3 D structures of CdGLUT4 and HsGLUT4 generated by homology modelling revealed conservation of characteristic signature motifs. CdGLUT4 was cloned and expressed optimally in C43(DE3)pLysS strain and maximum detergent solubility was observed in n-Dodecyl-β-d-maltopyranoside. These preliminary data provide information on residual differences between CdGLUT4 and HsGLUT4 that may be responsible for camel's unique glucose metabolism. These differences are postulated to assist in designing and development of efficacious GLUT4 that might help in management of diabetic patients.
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http://dx.doi.org/10.1080/13813455.2017.1312460DOI Listing
October 2017

Zika Virus-Induced Microcephaly and Its Possible Molecular Mechanism.

Intervirology 2016 13;59(3):152-158. Epub 2017 Jan 13.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.

Zika virus is an arthropod-borne re-emerging pathogen associated with the global pandemic of 2015-2016. The devastating effect of Zika viral infection is reflected by its neurological manifestations such as microcephaly in newborns. This scenario evoked our interest to uncover the neurotropic localization, multiplication of the virus, and the mechanism of microcephaly. The present report provides an overview of a possible molecular mechanism of Zika virus-induced microcephaly based on recent publications. Transplacental transmission of Zika viral infection from mother to foetus during the first trimester of pregnancy results in propagation of the virus in human neural progenitor cells (hNPCs), where entry is facilitated by the receptor (AXL protein) leading to the alteration of signalling and immune pathways in host cells. Further modification of the viral-induced TLR3-mediated immune network in the infected hNPCs affects viral replication. Downregulation of neurogenesis and upregulation of apoptosis in hNPCs leads to cell cycle arrest and death of the developing neurons. In addition, it is likely that the environmental, physiological, immunological, and genetic factors that determine in utero transmission of Zika virus are also involved in neurotropism. Despite the global concern regarding the Zika-mediated epidemic, the precise molecular mechanism of neuropathogenesis remains elusive.
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http://dx.doi.org/10.1159/000452950DOI Listing
March 2017

Co-Circulation of 72bp Duplication Group A and 60bp Duplication Group B Respiratory Syncytial Virus (RSV) Strains in Riyadh, Saudi Arabia during 2014.

PLoS One 2016 11;11(11):e0166145. Epub 2016 Nov 11.

School of Medicine, Center for Global Health, Colorado School of Public Health, Aurora, Colorado, United States of America.

Respiratory syncytial virus (RSV) is an important viral pathogen of acute respiratory tract infection (ARI). Limited data are available on molecular epidemiology of RSV from Saudi Arabia. A total of 130 nasopharyngeal aspirates were collected from children less than 5 years of age with ARI symptoms attending the Emergency Department at King Khalid University Hospital and King Fahad Medical City, Riyadh, Saudi Arabia between October and December, 2014. RSV was identified in the 26% of the hospitalized children by reverse transcriptase PCR. Group A RSV (77%) predominated during the study as compared to group B RSV (23%). The phylogenetic analysis of 28 study strains clustered group A RSV in NA1 and ON1 genotypes and group B viruses in BA (BA9) genotype. Interestingly, 26% of the positive samples clustered in genotypes with duplication in the G protein gene (ON1 for group A and BA for group B). Both the genotypes showed enhanced O-linked glycosylation in the duplicated region, with 10 and 2 additional sites in ON1 and BA respectively. Selection pressure analysis revealed purifying selection in both the ON1 and BA genotypes. One codon each in the ON1 (position 274) and BA genotypes (position 219) were positively selected and had high entropy values indicating variations at these amino acid positions. This is the first report describing the presence of ON1 genotype and the first report on co-circulation of two different genotypes of RSV with duplication in the G protein gene from Saudi Arabia. The clinical implications of the simultaneous occurrence of genotypes with duplication in G protein gene in a given population especially in the concurrent infections should be investigated in future. Further, the ongoing surveillance of RSV in this region will reveal the evolutionary trajectory of these two genotypes with duplication in G protein gene from largest country in the Middle East.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0166145PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106011PMC
July 2017

Evolutionary Analysis of Dengue Serotype 2 Viruses Using Phylogenetic and Bayesian Methods from New Delhi, India.

PLoS Negl Trop Dis 2016 Mar 15;10(3):e0004511. Epub 2016 Mar 15.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.

Dengue fever is the most important arboviral disease in the tropical and sub-tropical countries of the world. Delhi, the metropolitan capital state of India, has reported many dengue outbreaks, with the last outbreak occurring in 2013. We have recently reported predominance of dengue virus serotype 2 during 2011-2014 in Delhi. In the present study, we report molecular characterization and evolutionary analysis of dengue serotype 2 viruses which were detected in 2011-2014 in Delhi. Envelope genes of 42 DENV-2 strains were sequenced in the study. All DENV-2 strains grouped within the Cosmopolitan genotype and further clustered into three lineages; Lineage I, II and III. Lineage III replaced lineage I during dengue fever outbreak of 2013. Further, a novel mutation Thr404Ile was detected in the stem region of the envelope protein of a single DENV-2 strain in 2014. Nucleotide substitution rate and time to the most recent common ancestor were determined by molecular clock analysis using Bayesian methods. A change in effective population size of Indian DENV-2 viruses was investigated through Bayesian skyline plot. The study will be a vital road map for investigation of epidemiology and evolutionary pattern of dengue viruses in India.
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http://dx.doi.org/10.1371/journal.pntd.0004511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792444PMC
March 2016
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