Search results for "Dengue"

2015

ABSTRACT Dengue fever is a severe, widespread, and neglected disease with more than 2 million diagnosed infections per year. The dengue virus NS2B/NS3 protease (PR) represents a prime target for rational drug design. At the moment, there are no clinical PR inhibitors (PIs) available. We have identified diaryl (thio)ethers as candidates for a novel class of PIs. Here, we report the selective and noncompetitive inhibition of the serotype 2 and 3 dengue virus PR in vitro and in cells by benzothiazole derivatives exhibiting 50% inhibitory concentrations (IC 50 s) in the low-micromolar range. Inhibition of replication of DENV serotypes 1 to 3 was specific, since all substances influenced neither…

Lateral flow assays (LFA) as an alternative medical diagnosis method for detection of virus species: The intertwine of nanotechnology with sensing st…

2021

Viruses are responsible for multiple infections in humans that impose huge health burdens on individuals and populations worldwide. Therefore, numerous diagnostic methods and strategies have been developed for prevention, management, and decreasing the burden of viral diseases, each having its advantages and limitations. Viral infections are commonly detected using serological and nucleic acid-based methods. However, these conventional and clinical approaches have some limitations that can be resolved by implementing other detector devices. Therefore, the search for sensitive, selective, portable, and costless approaches as efficient alternative clinical methods for point of care testing (P…

Biochemistry and medicinal chemistry of the dengue virus protease.

2014

Proline-Based Allosteric Inhibitors of Zika and Dengue Virus NS2B/NS3 Proteases

2019

The NS2B/NS3 serine proteases of the Zika and Dengue flaviviruses are attractive targets for the development of antiviral drugs. We report the synthesis and evaluation of a new, proline-based compound class that displays allosteric inhibition of both proteases. The structural features relevant for protease binding and inhibition were determined to establish them as new lead compounds for flaviviral inhibitors. Based on our structure-activity relationship studies, the molecules were further optimized, leading to inhibitors with submicromolar IC50 values and improved lipophilic ligand efficiency. The allosteric binding site in the proteases was probed using mutagenesis and covalent modificati…

SAR of novel benzothiazoles targeting an allosteric pocket of DENV and ZIKV NS2B/NS3 proteases

2021

In recent years, dengue virus (DENV) and Zika virus (ZIKV), both mosquito-borne members of the Flaviviridae family, have emerged as intercontinental health issues since their vectors have spread from their tropical origins to temperate climate zones due to climate change and increasing globalization. DENV and ZIKV are positive-sense, single-stranded RNA viruses, whose genomes consist of three structural (capsid, membrane precursor, envelope) and seven non-structural (NS) proteins, all of which are initially expressed as a single precursor polyprotein. For virus maturation, the polyprotein processing is accomplished by host proteases and the viral NS2B/NS3 protease complex, whose inhibitors …

An epigenetic ‘extreme makeover’: the methylation of flaviviral RNA (and beyond)

2020

Beyond their high clinical relevance worldwide, flaviviruses (comprising dengue and Zika viruses) are of particular interest to understand the spatiotemporal control of RNA metabolism. Indeed, their positive single-stranded viral RNA genome (vRNA) undergoes in the cytoplasm replication, translation and encapsidation, three steps of the flavivirus life cycle that are coordinated through a fine-tuned equilibrium. Over the last years, RNA methylation has emerged as a powerful mechanism to regulate messenger RNA metabolism at the posttranscriptional level. Not surprisingly, flaviviruses exploit RNA epigenetic strategies to control crucial steps of their replication cycle as well as to evade sen…

Copper(II)-Binding Induces a Unique Polyproline Type II Helical Structure within the Ion-Binding Segment in the Intrinsically Disordered F-Domain of …

2019

Reproduction of the dominant vector of Zika and dengue diseases, Aedes aegypti mosquito, is controlled by an active heterodimer complex composed of the 20-hydroxyecdysone receptor (EcR) and ultraspiracle protein. Although A. aegypti EcR shares the structural and functional organization with other nuclear receptors, its C-terminus has an additional long F domain (AaFEcR). Recently, we showed that the full length AaFEcR is intrinsically disordered with the ability to specifically bind divalent metal ions. Here, we describe the details of the exhaustive structural and thermodynamic properties of Zn2+- and Cu2+-complexes with the AaFEcR domain, based on peptide models of its two putative metal …

Spatio-Temporal Modeling of Zika and Dengue Infections within Colombia

2018

The aim of this study is to estimate the parallel relative risk of Zika virus disease (ZVD) and dengue using spatio-temporal interaction effects models for one department and one city of Colombia during the 2015&ndash

Louseborne relapsing fever in young migrants, sicily, Italy, july-september 2015

2016

To the Editor: During the early 20th century, at the end of World War I, and during World War II, louseborne relapsing fever (LBRF) caused by Borrelia recurrentis was a major public health problem, especially in eastern Europe and northern Africa (1,2). Currently, poor living conditions, famine, war, and refugee camps are major risk factors for epidemics of LBRF in resource-poor countries, such as those in the Horn of Africa (3,4). Increased migration from resource-poor countries and war/violence create new routes for spread of vectorborne diseases. Recently, several cases of LBRF have been reported among asylum seekers from Eritrea in the Netherlands, Switzerland, and Germany (5–8). All of…

Editorial: Emerging Zoonoses: Eco-Epidemiology, Involved Mechanisms, and Public Health Implications

2015

Zoonoses are currently considered as one of the most important threats for Public Health worldwide. Zoonoses can be defined as any disease or infection that is naturally transmissible from vertebrate or invertebrate animals to humans and vice-versa. Approximately, 75% of recently emerging infectious diseases affecting humans are diseases of animal origin; approximately, 60% of all human pathogens are zoonotic. All types of potential pathogenic agents, including viruses, parasites, bacteria, and fungi, can cause these zoonotic infections. From the wide range of potential vectors of zoonoses, arthropods are probably those of major significance due to their abundance, high plasticity, adaptabi…