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Despite a huge number of studies towards vaccine development against human immunodeficiency virus-1, no effective vaccine has been approved yet. Thus, new vaccines should be provided with new formulations. Herein, a new DNA vaccine... more
Despite a huge number of studies towards vaccine development against human immunodeficiency virus-1, no effective vaccine has been approved yet. Thus, new vaccines should be provided with new formulations. Herein, a new DNA vaccine candidate encoding conserved and immunogenic epitopes from HIV-1 antigens of tat, pol, gag and env is designed and constructed. After bioinformatics analyses to find the best epitopes and their tandem, nucleotide sequence corresponding to the designed multiepitope was synthesized and cloned into pcDNA3.1+ vector. Expression of pcDNA3.1-tat/pol/gag/env plasmid was evaluated in HEK293T cells by RT-PCR and western-blotting. Seven groups of BALB/c mice were intramuscularly immunized three times either with 50, 100, 200 µg of plasmid in 2-week intervals or with similar doses of insert-free plasmid. Two weeks after the last injection, proliferation of T cells and secretion of IL4 and IFN-γ cytokines were evaluated using Brdu and ELISA methods, respectively. Results showed the proper expression of the plasmid in protein and mRNA levels. Moreover, the designed multiepitope plasmid was capable of induction of both proliferation responses as well as IFN-γ and IL-4 cytokine production in a considerable level compared to the control groups. Overall, our primary data warranted further detailed studies on the potency of this vaccine.
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An efficient vaccine against hepatitis-C virus (HCV) infection requires vigorous and focused CD8(+) T-cell responses against viral antigens. Due to immunosuppressive effect of HCV antigens, polytope vaccines comprising the minimal... more
An efficient vaccine against hepatitis-C virus (HCV) infection requires vigorous and focused CD8(+) T-cell responses against viral antigens. Due to immunosuppressive effect of HCV antigens, polytope vaccines comprising the minimal CD8(+)CTL epitopes are of peculiar concern. Herein, to provide information for construction of efficient HCV polytope vaccine candidates, one H-2D(d) (E2(405-414):E(2)) and two HLA-A*0201 (E1(363-372):E(1) and Core(35-44):C)-restricted CD8(+) T-cell epitopes of HCV were selected. By employing number of in silico analyses, the E(2)E(1)C linear format was predicted as optimum epitope consecution and after amplification by SOEing-PCR, the corresponding DNA sequence was cloned in pcDNA3.1+ vector. To further evaluate the role of immune-enhancer elements, a universal T-helper epitope (PADRE), endoplasmic reticulum signal sequence (ERss) and hepatitis-B surface-antigen (HBsAg) gene were fused separately or in combination to the E(2)E(1)C minigene. In vitro analyses of polytopes by different DNA/protein-based assays demonstrated proper transcription/expression of constructs in transfected cells. Measurement of the HBsAg-mediated particle secretion by ELISA indicated lack of secretion in the related polytopes. Results of delayed-type hypersensitivity (DTH) as a preliminary in vivo analysis, and confirmatory ELISPOT assays showed the proper processing and presentation of H-2D(d)-restricted-E(2) epitope and approved the enhancing effect of PADRE and ERss sequences but not HBsAg for the immune responses against E(2) in immunized BALB/c mice. Our results pointed to the value of in silico predictions and application of immune-enhancer elements as well as DTH analysis for design and primary in vivo evaluation of HCV polytopes, prior to costly transgenic studies on immunogenicity of HLA-A*0201 epitopes.
Research Interests: Immune response, Biology, Hepatitis C, Biological Sciences, Cercopithecus aethiops, and 15 moreHumans, Female, Animals, Endoplasmic Reticulum, Hepatitis C Virus, DNA vaccination, Amino Acid Sequence, In Silico, Immunogenicity, HBsAg, DNA sequence, Hepacivirus, epitope, Medical and Health Sciences, and Hepatitis B surface antigen
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Despite the worldwide efforts made in the field of HIV vaccine development, an efficient AIDS vaccine strategy is still vague. Virus-like particles (VLPs) are one of the introduced aspects for HIV vaccine development since the... more
Despite the worldwide efforts made in the field of HIV vaccine development, an efficient AIDS vaccine strategy is still vague. Virus-like particles (VLPs) are one of the introduced aspects for HIV vaccine development since the non-replicative nature of HIV VLPs, resulting from the lack of viral genomic RNA, makes them suitable for broad applications. We have previously designed and introduced non-infectious VLPs (mzNL4-3) by introduction of a deletion mutation in the reverse transcriptase and integrase coding regions of HV-1. There are evidences suggesting that an effective cellular immune response against HIV-1 is able to control and suppress viremia during primary and chronic HIV infections. In the present study we have evaluated the potency of mzNL4-3 VLPs mixed with Neisseria meningitidis serogroup B outer-membrane vesicle (OMV), which is among the microbial components with proved adjuvant properties, to induce humoral and cellular responses against HIV-1. Analysis of anti-HIV-1 responses elicited in immunized BALB/c mice following different immunization regimens indicated OMV+VLP as an immunopotent combination which significantly induced anti-HIV-1 IgG with IgG2a dominancy. Results of cytokine and ELISpot assays also showed the capability of VLP+OMV immunogen for effective induction of IFN-gamma; and IL4 secreting cells and further suggested the promotion of Th1-oriented response that was evidenced with the increased IFN-γ/IL4 secretion ratio. According to our study, HIV-1 VLPs combined with N. meningitidis B OMVs seem to be a promising approach in vaccine development against HIV-1.
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Human immunodeficiency virus infection is a worldwide health problem and a protective vaccine is desperately needed to control the AIDS pandemics. To address this concern, we previously constructed single-cycle replicable (SCR) HIV-1... more
Human immunodeficiency virus infection is a worldwide health problem and a protective vaccine is desperately needed to control the AIDS pandemics. To address this concern, we previously constructed single-cycle replicable (SCR) HIV-1 virions, which completely maintained the antigenic structures of HIV-1. Herein, to optimize a vaccination strategy, we studied the immunogenicity of produced SCR virions and adjuvant-formulated HIV-1 virus-like particles (VLPs) in homologous and heterologous prime-boosting regimens. Accordingly, BALB/c mice received three doses of immunogens in 3-week intervals and their immune responses were evaluated using ELISA, cytokine and IFN-γ ELISpot assays. These analyses not only indicated the superiority of SCR prime-VLP boosting for strong induction of specific IFN-γ producing cells, but also showed the capability of this strategy over the others for better stimulation of humoral response, which was evidenced with the detection of highest titer of total IgG against HIV ENV glycoprotein. Furthermore, determination of IgG subclasses and IFN-γ/IL4 secretion ratio in cultured splenocytes demonstrated the efficient augmentation of mixed responses with the dominancy of Th1 immunity following SCR/VLP immunization strategy. Our results additionally pointed towards the applicability of Montanide ISA 720 + CpG as a potent Th1-directing adjuvant mixture. Overall, this study suggests SCR prime-VLP boosting as a promising approach in HIV vaccine development.
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Research Interests: Microbiology, Medical Microbiology, Biology, Virology, Medicine, and 7 moreHIV, Humans, Mice, Animals, ACTA, HIV Integrase, and frameshift mutation
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Introduction: Thrombosis and the blockage of blood vessels with clots, can lead to acute myocardial infarction and
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Background: Due to the lack of efficient anti-HIV vaccine, anti-HIV pharmaceuticals play an important role in controlling HIV infection. Also significant rise in drug resistance and drug toxicity has caused increased interest in finding... more
Background: Due to the lack of efficient anti-HIV vaccine, anti-HIV pharmaceuticals play an important role in controlling HIV infection. Also significant rise in drug resistance and drug toxicity has caused increased interest in finding new anti-HIV agents. In this study, a nano-sized version of lamivudine based on PEGylated chitosan was synthesized. Materials and Methods: In this research, nanoparticles of chitosan were efficiently PEGylated for increasing their stability in water and then the anti-HIV drug, lamivudine, was loaded on these PEGylated nanoparticles. After purification and lyophilization of new synthesized nanoparticle, the raw materials and final product were sampled and FTIR, HNMR and CHN analyses were done. Results: Results of HNMR spectroscopy showed that chitosan nanoparticle was successfully PEGylated. HNMR data confirmed FTIR results and indicated that lamivudine was conjugated on chitosan nanoparticle. In addition, CHN analysis data also confirmed both HNMR an...
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BACKGROUND Given the lack of access to a full-length sequence of hepatitis A virus (HAV) and scarce information about its circulating genotype, sub-type and strain in Iran, two specimens were isolated from two patients with clinical... more
BACKGROUND Given the lack of access to a full-length sequence of hepatitis A virus (HAV) and scarce information about its circulating genotype, sub-type and strain in Iran, two specimens were isolated from two patients with clinical symptoms of acute HAV to determine the full-length sequence of HAV. Following the phylogenetic and molecular study, we determined HAV genotype, sub-genotype, and strain of circulating virus in Iran. METHODS According to real-time PCR results, 16 pairs of overlapped specific primers were used to determine the full-length sequence of HAV by whole-genome amplification (WGA) and using the Sanger method. Moreover, the results were assessed using Chromas, CLC Genomics Workbench, Mega 6, and RDP software. RESULTS The full-length genome of HAV was amplified and sequenced with a length of 7,182 nucleotides. According to the obtained sequences, the phylogenetic tree of the mentioned viruses was drawn using MEGA 6 software and 44 full-genome viruses registered in the GenBank worldwide. Afterwards, the same process was repeated based on the protein sequence of VP1-P2A fragment in Iranian samples along with the other 22 registered protein sequences of GenBank to confirm the results of the full-genome phylogenetic tree. CONCLUSIONS In this study, complete sequencing of two HAV specimens was carried out using the overlapping amplification and Sanger methods. According to the results of the phylogenetic tree, the circulating HAV in Iran had Genotype I and sub-genotype B and strain HM-175. In the present study, the full sequences of HAV of the two specimens were registered with accession numbers of BankIt 2277890/MN746031 and BankIt 2287607/MN746032.
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Background: Homeless people are at a higher risk of blood-born infectious diseases. The aim of this study was to estimate the prevalence of HIV, HBV, HCV and related risk factors among male homeless people. Study design: A cross-sectional... more
Background: Homeless people are at a higher risk of blood-born infectious diseases. The aim of this study was to estimate the prevalence of HIV, HBV, HCV and related risk factors among male homeless people. Study design: A cross-sectional study. Methods: This study was conducted in Khorramabad City, western Iran from January to June 2015. A pre-designed validated questionnaire was used to collect the data on behavioral and other potential risk factors. Blood samples were taken in order to diagnose HIV, hepatitis B and C infections. The prevalence of HIV, hepatitis B, C and related risk factors was reported with a 95% confidence interval (CI). Results: The participants were 307 male homeless people with a mean (±SD) age of 35.86 (±9.62) yr. The prevalence of HIV, HBs Ag, and HCV Ab positive cases was 6.51% (95% CI: 4.23, 9.90), 0.98% (95% CI: 0.31, 3.00), and 31.27% (26.31, 36.71), respectively. The prevalence of co-infections of HIV and HCV Ab+ was 5.76% (95% CI: 1.34, 8.51). The mo...
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Objective(s) The aim of this study was to evaluate the effects of dexamethasone on striatal dopaminergic, glutamatergic and gamma amino butyric acid (GABA) ergic neurotransmission in normal and parkinsonian rats. Materials and Methods... more
Objective(s) The aim of this study was to evaluate the effects of dexamethasone on striatal dopaminergic, glutamatergic and gamma amino butyric acid (GABA) ergic neurotransmission in normal and parkinsonian rats. Materials and Methods Dexamethasone (0.15, 0.30, 0.60 and 0.8 mg/kg) was administered to normal or parkinsonian rats (i.p.) followed by the analysis of the striatal neurotransmitters concentrations. Additionally, the effect of dexamethasone on the damaged Substantia nigra pars compata (SNc) neurons has been investigated. Results Dexamethasone resulted in decreased level of striatum glutamatergic-GABAergic and enhanced dopaminergic neurotransmission in normal and parkinsonian rats. In addition, acute treatment with dexamethasone did not improve the lesion at all. Conclusion These findings suggest the new therapeutic mechanism of action for dexamethasone in Parkinson’s disease animal model.
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Application of streptokinase (SK) as a common and cost-effective thrombolytic drug is limited by its antigenicity and undesired hemorrhagic effects. Prior structural/functional and epitope-mapping studies on SK suggested that removal of... more
Application of streptokinase (SK) as a common and cost-effective thrombolytic drug is limited by its antigenicity and undesired hemorrhagic effects. Prior structural/functional and epitope-mapping studies on SK suggested that removal of 59 N-terminal residues led to its fibrin dependency and identified SK antigenic regions, respectively. Following in silico analyses two truncated SK proteins were designed and compared for their fibrin specificity and antigenicity with the full-length SK. Computer-based modeling was used to predict the effect of vector (pET41a)-born protein tags on the conformation of SK fragments. SK60-386, SK143-386 and full-length SK (1-414) were separately cloned, expressed in BL21 E. coli cells and confirmed by Western-blotting. Functional activity of the purified proteins was evaluated with chromogenic and clot lysis assays and their antigenicity was tested by ELISA assay using rabbit anti-streptokinase antibody. As expected, chromogenic bioassay showed a major...
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The structural similarities between N1 substituted 1,4-dihydropyridines and the known gp41 inhibitors, NB-2 and NB-64, were considered in the current research for the design of some novel anti-HIV-1 agents. A series of novel... more
The structural similarities between N1 substituted 1,4-dihydropyridines and the known gp41 inhibitors, NB-2 and NB-64, were considered in the current research for the design of some novel anti-HIV-1 agents. A series of novel 4-[4-arylpyridin-1(4H)-yl]benzoic acid derivatives were synthesized and after a comprehensive structural elucidation were screened for in vitro anti-HIV-1 activity. Most of the tested compounds displayed moderate to good inhibitory activity against HIV-1 growth and were evaluated for in vitro cytotoxic activity using XTT assay at the concentration of 100 μm. Among the tested compounds, 1c, 1d and 1e showed potent anti-HIV-1 activity against P24 expression at 100 μm with inhibition percentage of 84.00%, 76.42% and 80.50%, respectively. All the studied compounds possessed no significant cytotoxicity on MT-2 cell line. The binding modes of these compounds to gp41 binding site were determined through molecular docking study. Docking studies proved 1a as the most pot...
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To provide more accurate estimates of the prevalence of Hepatitis B (HBV) and Hepatitis C (HCV) and their contributing factors among prisoners in Iran. Cross-sectional study of 6200 Iranian prisoners in 2015. Data were collected through... more
To provide more accurate estimates of the prevalence of Hepatitis B (HBV) and Hepatitis C (HCV) and their contributing factors among prisoners in Iran. Cross-sectional study of 6200 Iranian prisoners in 2015. Data were collected through questionnaires and interviews. HBV infection and HCV exposure status of the participants was determined by HBsAg and HCV antibodies blood tests using Enzyme-Linked Immunosorbent Assay (ELISA). Data were analyzed in STATA-12. Prevalence of HCV exposure was 9.48% (95% CI: 8.73-10.27) and prevalence of HBV was 2.48% (95% CI: 2.07-2.89) in the general prison population. In multivariate analysis, the most important risk factor for HBV was a history of drug use in lifetime (AOR: 1.8, 95% CI: 1.17-3.02). The main risk factors for HCV exposure were a history of drug use in lifetime (AOR: 4.08, CI: 2.56-6.27), age over 30 (AOR: 2.68, CI: 2.01-3.56), and having tattoos (AOR=1.67, CI: 1.35-2.07). Although vaccination is used to control HBV among prisoners, prev...
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Research Interests: Treatment Outcome, Medicine, Iran, Humans, Female, and 15 moreMale, Middle Aged, Adult, Public health systems and services research, Interleukins, Combination drug therapy, Base Sequence, Recombinant Proteins, chronic hepatitis C, Polyethylene Glycols, Ribavirin, Antiviral Agents, Interferon Alpha, Hepacivirus, and alleles
Chemotherapy, a conventional method assessed in recent oncology studies, poses numerous problems in the clinical environment. To overcome the problems inherent in chemotherapy, an intelligent drug delivery system has come to the forefront... more
Chemotherapy, a conventional method assessed in recent oncology studies, poses numerous problems in the clinical environment. To overcome the problems inherent in chemotherapy, an intelligent drug delivery system has come to the forefront of cancer therapeutics. In this study, we designed a dendrimer-based pharmaceutical system together with a single-stranded AS1411 aptamer (APT(AS)(1411) ) as a therapeutic strategy. The polyamidoamine (PAMAM)-polyethylene glycol (PEG) complex was then conjugated with the AS1411 aptamer and confirmed by atomic-force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR) .In this study, we show that the conjugated PAMAM-PEG-APT(AS)(1411) complex dramatically increased PAMAM-PEG-5-FU uptake by MKN45 gastric cancer cells. We also demonstrated both the stability of the nanoparticle-5-FU-APT(AS)(1411) complex, by thin layer chromatography (TLC), and an increase in 5-fluorouracil (5-FU) accumulation in the vicinity of cancerous tumors. This smart drug delivery system is capable of effectively transferring 5-FU to MKN45 gastric cancer cells in consistent and without toxic effects.
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A nationwide hepatitis B virus (HBV) vaccination program for neonates was launched in Iran in 1993. Despite the success of this program, concern about its long-term success still remains, because breakthrough infections due to emergence... more
A nationwide hepatitis B virus (HBV) vaccination program for neonates was launched in Iran in 1993. Despite the success of this program, concern about its long-term success still remains, because breakthrough infections due to emergence of surface mutants have been reported in immunized children. We aimed to evaluate the seroprevalence of HBV and vaccine escape mutants among individuals born after the initiation of the nationwide vaccination program in Iran. This study included 1115 participants younger than 23 years old, with 223 in each age cohort. The presence of HBsAg, anti-HBs and anti-HBc was evaluated using an ELISA kit. HBV-DNA levels were measured in anti-HBc and/or HBsAg-positive subjects. PCR products were sequenced and mutations were identified. The overall HBsAg prevalence was 0.27 %. Anti-HBs and anti-HBc positive rates were 48 % and 0.18 %, respectively. Two individuals were positive for anti-HBc, one of whom was also positive for HBsAg, and the other was positive for...
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Hap, an auto-transporter protein, is an antigenically conserved adhesion protein which is present on both typeable and nontypeable Haemophilus influenzae. This protein has central role in bacterial attachment to respiratory tract... more
Hap, an auto-transporter protein, is an antigenically conserved adhesion protein which is present on both typeable and nontypeable Haemophilus influenzae. This protein has central role in bacterial attachment to respiratory tract epithelial cells. A 1000bp C-terminal fragment of Hap passenger domain (HapS) from nontypeable Haemophilus influenzae was cloned into a prokaryotic expression vector, pET-24a. BALB/c mice were immunized subcutaneously with purified rC-HapS. Serum IgG responses to purified rC-HapS, serum IgG subclasses were determined by ELISA and functional activity of antibodies was examined by Serum Bactericidal Assay. The output of rC-HapS was approximately 62% of the total bacterial proteins. Serum IgG responses were significantly increased in immunized group with rC-HapS mixed with Freund's adjuvant in comparison with control groups. Analysis of the serum IgG subclasses showed that the IgG1 subclass was predominant after subcutaneous immunization in BALB/c mice (IgG2a/IgG1 < 1). The sera from rC-HapS immunized animals were strongly bactericidal against nontypeable Haemophilus influenzae. These results suggest that rC-HapS may be a potential vaccine candidate for nontypeable Haemophilus influenzae.
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BACKGROUND Hepatitis C virus as a major cause of chronic liver disease affects more than 170 million people worldwide. Recent studies have claimed that single nucleotide polymorphisms (SNPs) for the transforming growth factor-β1 (TGF-β1)... more
BACKGROUND Hepatitis C virus as a major cause of chronic liver disease affects more than 170 million people worldwide. Recent studies have claimed that single nucleotide polymorphisms (SNPs) for the transforming growth factor-β1 (TGF-β1) gene were strongly associated with the antiviral treatment response. Thus, the present study aimed at the determination of distribution of the rs1800469 (C/T) polymorphism among Iranian with chronic hepatitis C. METHODS A total of 165 blood samples including 68 SVR positive and 21 non-responder samples from individuals suffering chronic hepatitis C and also 76 healthy individual controls were analyzed in this cross-sectional study. DNA was isolated from the samples using a DNA extraction standard kit. Then the frequency of the polymorphism was analyzed using PCR-RFLP method. Eventually, the products of interest were detected on 2.5% agarose gel electrophoresis. RESULTS The distribution of the C/T polymorphism between healthy individuals and patients were obtained as TT: 22.4%, TC: 46%, CC: 31.6%, and TT: 19.1%, TC: 48.3%, CC: 32.6%, respectively. Furthermore, the CC genotype was identified in 20 patients of whom 68 achieved SVR, while the CT heterozygous was found in 43 patients and SVR was achieved in 38. Finally, the TT was detected in 17 patients, and 7 patients did not achieve SVR. CONCLUSIONS We observed a significant difference of C allele frequency with SVR as compared to the T allele among patients (p = 0.064). On the other hand, there is no correlation between the polymorphism and susceptibility to HCV infection. However, further studies with more samples seem to be necessary.
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It seems that the success of vaccination for cancer immunotherapy such as Dendritic Cell (DC) based cancer vaccine is hindered through a powerful network of immune system suppressive elements in which regulatory T cell is the common... more
It seems that the success of vaccination for cancer immunotherapy such as Dendritic Cell (DC) based cancer vaccine is hindered through a powerful network of immune system suppressive elements in which regulatory T cell is the common factor. Foxp3 transcription factor is the most specific marker of regulatory T cells. In different studies, targeting an immune response against regulatory cells expressing Foxp3 and their removal have been assessed. As these previous studies could not efficiently conquer the suppressive effect of regulatory cells by their partial elimination, an attempt was made to search for constructing more effective vaccines against regulatory T cells by which to improve the effect of combined means of immunotherapy in cancer. In this study, a DNA vaccine and its respective protein were constructed in which Foxp3 fused to Fc(IgG) can be efficiently captured and processed by DC via receptor mediated endocytosis and presented to MHCII and I (cross priming). DNA constr...
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The rapid increase of HIV-1 strains resistant to current antiretroviral drugs is a challenge for successful AIDS therapy. This necessitates the development of novel drugs, and to this end, availability of screening systems for in vitro... more
The rapid increase of HIV-1 strains resistant to current antiretroviral drugs is a challenge for successful AIDS therapy. This necessitates the development of novel drugs, and to this end, availability of screening systems for in vitro drug discovery is a priority. Herein, we report the modification of a previously developed system for increased sensitivity, ease of use, and cost-efficiency, based on the application of the EGFP marker. A PCR-amplified gfp gene (gfp) was cloned into pmzNL4-3, the plasmid already designed to produce single-cycle replicable virions, in frame with the reverse-transcriptase gene to construct the pmzNL4-3/GFP plasmid. GFP-mzNL4-3 pseudo-typed virions, as the first progeny viruses, were recovered from the culture supernatant of HEK293T cells co-transfected with pmzNL4-3/GFP and the helper plasmids pSPAX2 and pMD2G, which respectively encode HIV-1 Gag-Pol and vesicular stomatitis virus glycoprotein. Single-cycle replication and virion production were assess...
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Hepatitis C virus (HCV) infection is a serious public health threat worldwide. Cellular immune responses, especially cytotoxic T-lymphocytes (CTLs), play a critical role in immune response toward the HCV clearance. Since polytope vaccines... more
Hepatitis C virus (HCV) infection is a serious public health threat worldwide. Cellular immune responses, especially cytotoxic T-lymphocytes (CTLs), play a critical role in immune response toward the HCV clearance. Since polytope vaccines have the ability to stimulate the cellular immunity, a recombinant fusion protein was developed in this study. The designed fusion protein is composed of hepatitis B surface antigen (HBsAg), as an immunocarrier, fused to an HCV polytope sequence. The polytope containing five immunogenic epitopes of HCV was designed to induce specific CTL responses. The construct was cloned into the pET-28a, and its expression was investigated in BL21 (DE3), BL21 pLysS, BL21 pLysE, and BL21 AI Escherichia coli strains using 12% gel sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Finally, the identity of expressed fusion protein was confirmed by Western blotting using anti-His monoclonal antibody and affinity chromatography was applied to purify the expres...
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A series of 5-hydroxypyridine-4-one derivatives were synthesized and subjected to HIV-1 replication inhibition assay. Docking studies provide a detailed molecular binding model for this class of compounds interacting with integrase... more
A series of 5-hydroxypyridine-4-one derivatives were synthesized and subjected to HIV-1 replication inhibition assay. Docking studies provide a detailed molecular binding model for this class of compounds interacting with integrase enzyme. All of the derivatives were recognized potent in the docking studies in terms of both the estimated free energy change of binding and interactions with integrase key elements. 5a, 5c, 5d, 5h and 5n exhibited good anti-HIV-1 activities in cell-based assay. Compound 5d was the most potent derivative not only in vitro but also in silico. 5c and 5h offered the highest therapeutic indices. Suboptimal lipophilicity of 6b, 6g, 6i, 6j, 6l and 5m made them inactive in assays, despite the high activity in the docking studies.
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Nontypeable Haemophilus influenzae (NTHi) is a common cause of respiratory tract disease and initiates infection by colonization in nasopharynx. The Haemophilus influenzae (H. influenzae) Hap adhesin is an auto transporter protein that... more
Nontypeable Haemophilus influenzae (NTHi) is a common cause of respiratory tract disease and initiates infection by colonization in nasopharynx. The Haemophilus influenzae (H. influenzae) Hap adhesin is an auto transporter protein that promotes initial interaction with human epithelial cells. Hap protein contains a 110 kDa internal passenger domain called "HapS" and a 45 kDa C-terminal translocator domain called "Hapβ". Hap adhesive activity has been recently reported to be connected to its Cell Binding Domain (CBD) which resides within the 311 C-terminal residues of the internal passenger domain of the protein. Furthermore, immunization with this CBD protein has been shown to prevent bacterial nasopharynx colonization in animal models. To provide enough amounts of pure HapS protein for vaccine studies, we sought to develop a highly optimized system to overexpress and purify the protein in large quantities. To this end, pET24a-cbd plasmid harboring cbd sequence f...
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ABSTRACT Inhibition of gp41 protein was proposed as a possible mechanism for the anti-HIV-1 properties of some 4-aryl-1,2,3,4-tetrahydropyrimidine-2(1H)-one (thione) derivatives. Two different in silico approaches, namely quantitative... more
ABSTRACT Inhibition of gp41 protein was proposed as a possible mechanism for the anti-HIV-1 properties of some 4-aryl-1,2,3,4-tetrahydropyrimidine-2(1H)-one (thione) derivatives. Two different in silico approaches, namely quantitative structure activity relationship (QSAR) and molecular docking studies were performed to characterize the relation between the structural features and the anti-HIV-1 activity and investigating the mode of interaction of the compounds with gp41. In the QSAR approach, free least squares support vector machine was used to derive a non-linear model based on the most important descriptors responsible for the activity of the compounds selected by stepwise multiple linear regression method. Docking results proved that the studied molecules have the optimum key interactions including hydrogen bonding, hydrophobic, electrostatic, π–π and cation–π interactions with the specific inhibitor binding site of gp41.