NS3 protease from flavivirus as a target for designing antiviral inhibitors against dengue virus

The development of novel therapeutic agents is essential for combating the increasing number of cases of dengue fever in endemic countries and among a large number of travelers from non-endemic countries. The dengue virus has three structural proteins and seven non-structural (NS) proteins. NS3 is a multifunctional protein with an N-terminal protease domain (NS3pro) that is responsible for proteolytic processing of the viral polyprotein, and a C-terminal region that contains an RNA triphosphatase, RNA helicase and RNA-stimulated NTPase domain that are essential for RNA replication. The serine protease domain of NS3 plays a central role in the replicative cycle of dengue virus. This review discusses the recent structural and biological studies on the NS2B-NS3 protease-helicase and considers the prospects for the development of small molecules as antiviral drugs to target this fascinating, multifunctional protein

Emergence of the Asian 1 Genotype of Dengue Virus Serotype 2 in Viet Nam: In Vivo Fitness Advantage and Lineage Replacement in South-East Asia

A better description of the extent and structure of genetic diversity in dengue virus (DENV) in endemic settings is central to its eventual control. To this end we determined the complete coding region sequence of 187 DENV-2 genomes and 68 E genes from viruses sampled from Vietnamese patients between 1995 and 2009. Strikingly, an episode of genotype replacement was observed, with Asian 1 lineage viruses entirely displacing the previously dominant Asian/American lineage viruses. This genotype replacement event also seems to have occurred within DENV-2 in Thailand and Cambodia, suggestive of a major difference in viral fitness. To determine the cause of this major evolutionary event we compared both the infectivity of the Asian 1 and Asian/American genotypes in mosquitoes and their viraemia levels in humans. Although there was little difference in infectivity in mosquitoes, we observed significantly higher plasma viraemia levels in paediatric patients infected with Asian 1 lineage viruses relative to Asian/American viruses, a phenotype that is predicted to result in a higher probability of human-to-mosquito transmission. These results provide a mechanistic basis to a marked change in the genetic structure of DENV-2 and more broadly underscore that an understanding of DENV evolutionary dynamics can inform the development of vaccines and anti-viral drugs

Sulfated Polysaccharide, Curdlan Sulfate, Efficiently Prevents Entry/Fusion and Restricts Antibody-Dependent Enhancement of Dengue Virus Infection In Vitro: A Possible Candidate for Clinical Application

10.1371/journal.pntd.0002188PLoS Neglected Tropical Diseases74

Comparison of central corneal thickness measurements with the Galilei dual Scheimpflug analyzer and ultrasound pachymetry

<b>Purpose:</b> To compare corneal pachymetry assessment by the Galilei dual Scheimpflug analyzer with that done by ultrasound (US) pachymetry. <b>Materials and Methods:</b> Forty six patients (92 eyes) were subjected to corneal pachymetry assessment by Galilei dual Scheimpflug analyzer and US. All the readings were taken by a single operator. Intraoperator repeatability for the Galilei was assessed by taking 10 readings in one eye each of 10 patients. To study the interoperator reproducibility for the Galilei, two observers took a single reading in both the eyes of 25 patients. <b>Results:</b> The mean central corneal thickness (CCT) measured by US was 541.83 &#177; 30.56 &#956;m standard deviation (SD) and that measured by Galilei was 541.27 &#177; 30.07 &#956;m (SD). There was no statistically significant difference between both the methods (<i>P</i> &lt; 0.001). The coefficient of repeatability was 0.43&#x0025; while the coefficient of reproducibility was 0.377&#x0025; for the Galilei. <b>Conclusion:</b> Objective, noncontact measurement of the CCT with the Galilei dual Scheimpflug analyzer was convenient, had excellent intraoperator repeatability and interoperator reproducibility, and findings were similar to those obtained with standard US pachymetry

Dengue virus life cycle:viral and host factors modulating infectivity

Dengue virus (DENV 1-4) represents a major emerging arthropod-borne pathogen. All four DENV serotypes are prevalent in the (sub) tropical regions of the world and infect 50-100 million individuals annually. Whereas the majority of DENV infections proceed asymptomatically or result in self-limited dengue fever, an increasing number of patients present more severe manifestations, such as dengue hemorrhagic fever and dengue shock syndrome. In this review we will give an overview of the infectious life cycle of DENV and will discuss the viral and host factors that are important in controlling DENV infection