Design, construction and evaluation of 1a/JFH1 HCV chimera by replacing the intergenotypic variable region

Peer reviewedPublisher PD

The Use of Microalgae for Coupling Wastewater Treatment With CO2 Biofixation

Production and emission of CO2 from different sources have caused significant changes in the climate, which is the major concern related to global warming. Among other CO2 removal approaches, microalgae can efficiently remove CO2 through the rapid production of algal biomass. In addition, microalgae have the potential to be used in wastewater treatment. Although, wastewater treatment and CO2 removal by microalgae have been studied separately for a long time, there is no detailed information available on combining both processes. In this review article, microalgae-based CO2 biofixation, various microalgae cultivation systems,̄ and microalgae-derived wastewater treatment are separately discussed, followed by the concept of integration of CO2 biofixation process and wastewater treatment. In each section, details of energy efficiency and differences across microalgae species are also given

Lentinan and β-glucan extract from shiitake mushroom, Lentinula edodes, alleviate acute LPS-induced hematological changes in mice

Objective(s): Immunomodulatory activity of β-glucans of shiitake mushroom (Lentinula edodes) has been known. We investigated whether β-glucans from L. edodes would attenuate the acute effects of lipopolysaccharides (LPS) on peripheral hematological parameters in mice.Materials and Methods: An in-house β-glucans extract (BG) prepared from fruiting bodies of shiitake mushroom L. edodes was chemically measured and characterized using spectrophotometry and HPLC. Male BALB/c mice directly inhaled aerosolized LPS of 3 mg/ml and were treated with BG or commercial β-glucan (known as lentinan; LNT) (10 mg/kg bw) at 1 hr before or 6 hr after LPS inhalation. The blood samples were collected by cardiac puncture from euthanized mice at 16 hr post-treatment. Results: The results showed a significant reduction in levels of blood parameters, including red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), and platelets (PLT); and a significant increase in blood lymphocyte counts in LPS-treated mice as compared with the control mice (P≤0.05). Total white blood cells, neutrophils, and monocyte counts did not show any significant difference among the groups. Treatment of LPS-challenged mice with LNT or BG significantly increased the levels of RBC, HGB, HCT, and PLT; and reduced blood lymphocyte counts as compared with LPS-treated mice (P≤0.05).Conclusion: These findings suggest that β-glucans from L. edodes might be effective in attenuating the effects of inhaled LPS on peripheral blood parameters. Thus, these findings might be useful in acute inflammatory diseases particularly pulmonary infectious diseases in which the hematological parameters would be affected

Structure-activity relationship studies on a Trp dendrimer with dual activities against HIV and enterovirus A71. Modifications on the amino acid

Supplementary data related to this article can be found at http:// dx.doi.org/10.1016/j.antiviral.2016.12.010.We have recently described a new class of dendrimers with tryptophan (Trp) on the surface that show dual antiviral activities against HIV and EV71 enterovirus. The prototype compound of this family is a pentaerythritol derivative with 12 Trps on the periphery. Here we complete the structure-activity relationship studies of this family to identify key features that might be significant for the antiviral activity. With this aim, novel dendrimers containing different amino acids (aromatic and non-aromatic), tryptamine (a “decarboxylated” analogue of Trp) and N-methyl Trp on the periphery have been prepared. Dendrimer with N-Methyl Trp was the most active against HIV-1 and HIV-2 while dendrimer with tyrosine was endowed with the most potent antiviral activity against EV71. This tyrosine dendrimer proved to inhibit a large panel of EV71 clinical isolates (belonging to different clusters) in the low nanomolar/high picomolar range. In addition, a new synthetic procedure (convergent approach) has been developed for the synthesis of the prototype and some other dendrimers. This convergent approach proved more efficient (higher yields, easier purification) than the divergent approach previously reported.This work has been supported by the Spanish MINECO [projects SAF2012-39760-C02 and SAF2015-64629-C2-1-R (MINECO/ FEDER)], “The Centers of Excellence” of the KU Leuven (EF-05/15 and PF-10/18), EU FP7 (FP7/2007e2013) Project EUVIRNA (Grant 408 Agreement 264286), EU FP7 SILVER (Contract HEALTH-F3- 2010-260644), a grant from the Belgian Interuniversity Attraction Poles (IAP) Phase VIIeP7/45 (BELVIR) and the EU FP7 Industry- Academia Partnerships and Pathways Project AIROPICO. The Spanish MEC/MINECO is also acknowledged for a grant to B.M.G and E.R. and the China Scholarship Council (CSC) (Grant 201403250056) for a grant to L.S. We also thank Charlotte Vanderheydt and Evelyne Van Kerckhove for help with the processing of the antiviral data.Peer Reviewe

Cross-reactive neutralizing antibody epitopes against Enterovirus 71 identified by an in silico approach

Currently, infections of hand, foot and mouth disease HFMD) due to Human Enterovirus 71 (EV71) cannot be prevented or treated, as there are no suitable vaccines or antiviral drugs. This study aimed to identify potential vaccine candidates for EV71 using in silico analysis of its viral capsid proteins. A combined in silico approach utilizing computational hidden Markov model (HMM), propensity scale algorithm, and artificial learning, identified three 15-mer structurally conserved B-cell epitope candidates lying within the EV71 capsid proteins. Peptide vaccine candidates incorporating a target B-cell epitope and a promiscuous T-cell epitope from the related polio virus were synthesized using solid-phase Fmoc chemistry. Inbred BALB/C mice which were inoculated with two 10μg doses of the synthetic peptide, generated anti-peptide antibodies. Purified IgG isolated from pooled sera of the inoculated mice neutralized EV71 infections in vitro. Furthermore, these neutralizing antibodies were cross-reactive against other members of the Picornaviridae family, demonstrating greater than 50% virus neutralization. This indicates that the current approach is promising for the development of synthetic peptide-based vaccine candidates against Picornaviridae. Development of effective vaccines is of paramount importance in managing the disease in the Asia Pacific regions where this virus is endemic and has significant social, economic and public health ramifications

Characterization of anti-enteroviral activity of heparan sulphate mimetic compounds

Enterovirus 71 (EV71) infection remains a public health problem at a global level, particularly in the Asia-pacific region. The infection normally manifests as hand-foot-mouth disease (HFMD); however, it is capable of developing into potentially fatal neurological complications. There is currently no approved vaccine or antiviral substance available for prevention or treatment of EV71 infection. There has been no research undertaken to examine the possible antiviral activity of heparan sulphate (HS) mimetics against the Human Enterovirus A (HEV-A), in particular EV71. Therefore, this PhD research began with the aim of investigating the antiviral potencies of HS mimetics against EV71 infection. Initially, a colorimetric-based method was developed for the titration of EV71 strains, whereby the viral titre was quantified more precisely. Three soluble HS mimetics including heparin (Hep), HS, and pentosan polysulphate (PPS) were then shown to substantially inhibit a cloned strain of EV71 from infecting in Vero cells. Further investigations revealed that the compounds most likely exerted their antiviral action through interference with the EV71 attachment. The role of cell surface HS in mediating viral infection was then studied for several clinical isolates of HEV-A and HEV-B in Vero cells as well as a human neuroblastoma cell line, SK-N-SH. The findings revealed that the clinical isolate of EV71 utilizes low sulphated domains of cellular HS to bind to Vero cells, in contrast to Coxsackievirus B4 (CVB4), Coxsackievirus A16 (CVA16), and the cloned EV71. In the neural cells, Hep and PPS significantly prevented both clinical EV71 and clinical CVA16 binding and infections, although it could not be confirmed whether the viruses utilize cellular HS to bind to the cells. Finally, an Affymetrix DNA microarray was performed to gain insight into the mechanisms of action of Hep against the clinical EV71 infection in the neural cells. The results showed many genes with significant down- or up-regulation across the undermentioned conditions: negative control cells, compound control (cells treated with Hep only), virus control (cells treated with virus only), and treatment control (EV71-infected cells treated with Hep). Several genes were finally found to be targets for the anti-EV71 activity of Hep in SK-N-SH cells using a strict multi-level selection procedure. In parallel, the results revealed the significant induction of more than 1000 genes by EV71 infection with expression fold changes ranged from +46.5 to -10.7. The findings of this research may suggest new directions for studies of designing molecular drug targets against EV71 infection

Development of antiviral agents toward Enterovirus 71 infection

Enterovirus 71 (EV71) infection remains a public health problem at a global level, particularly in the Asia-Pacific region. The infection normally manifests as hand-foot-mouth disease; however, it is capable of developing into potentially fatal neurological complications. There is currently no approved vaccine or antiviral substance available for the prevention or treatment of EV71 infection. This paper, thus, reviews efforts to develop or discover synthetic as well as naturally occurring compounds directed against EV71 infection. The recent achievements in cellular receptors of EV71 are also highlighted, and their contribution to the development of antiviral drugs against EV71 is discussed in this article

Global impact of Heparin on gene expression profiles in neural cells infected by Enterovirus 71

Objectives: Heparan sulphate mimetics, particularly heparin (Hep), have previously been shown to considerably inhibit infection of enterovirus 71 (EV71) in Vero cells. Therefore, in this study, a genome-wide DNA microarray was performed to gain insight into the mechanism(s) of action of Hep against infection of a human neural cell line, SK-N-SH, with a clinical strain of EV71. Methods: This study focused on a selection of EV71-induced genes whose expression profiling was exclusively affected by the antiviral activity of Hep. The selection procedure was performed through a statistical multi-level comparison with the following controls: negative control cells, compound control (cells treated with Hep only), virus control (cells treated with virus only) and treatment control (EV71-infected cells treated with Hep). Results: Overall, of more than 30,000 genes studied, 14 well-known annotated genes were selected that may be targets for the antiviral activity of Hep against EV71 infection in neural cells. For most of these genes, Hep appeared to modulate the impact of EV71 infection on the expression pattern of the genes. Conclusions: The findings of this research may provide initial assistance in new directions for studies to design molecular drug targets against EV71 infection. (C) 2013 S. Karger AG, Base