[Introduction to the antivirals against Dengue virus].

Dengue virus (DENV) is part of the Flaviviridae family and has been classify by the Word Health Organization (WHO) as one of the top 10 health concerns. It is the most widespread mosquito-borne human disease. Considering the increasing number of severe dengue, the expansion of the vector territory due to climate change and population movement, it is urgent to find a way to counteract the virus.

A broad-spectrum antiviral molecule, QL47, selectively inhibits eukaryotic translation.

Small-molecule inhibitors of translation are critical tools to study the molecular mechanisms of protein synthesis. In this study, we sought to characterize how QL47, a host-targeted, small-molecule antiviral agent, inhibits steady-state viral protein expression. We demonstrate that this small molecule broadly inhibits both viral and host protein synthesis and targets a translation step specific to eukaryotic cells.

Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells.

Zika virus (ZIKV) invades and persists in the central nervous system (CNS), causing severe neurological diseases. However the virus journey, from the bloodstream to tissues through a mature endothelium, remains unclear. Here, we show that ZIKV-infected monocytes represent suitable carriers for viral dissemination to the CNS using human primary monocytes, cerebral organoids derived from embryonic stem cells, organotypic mouse cerebellar slices, a xenotypic human-zebrafish model, and human fetus brain samples.

Structure-Activity Relationship Study of QL47: A Broad-Spectrum Antiviral Agent.

Here we report the structure-activity relationship (SAR) investigations of QL-XII-47 (QL47), a compound that possesses broad-spectrum antiviral activity against dengue virus and other RNA viruses. A medicinal chemistry campaign initiated from QL47, a previously reported covalent BTK inhibitor, to derive YKL-04-085, which is devoid of any kinase activity when screened against a panel of 468 kinases and with improved pharmacokinetic properties. Both QL47 and YKL-04-085 are potent inhibitors of viral translation and exhibit cellular antiviral activity at 35-fold lower concentrations relative to inhibition of host-cell proliferation.

Discovery of host-targeted covalent inhibitors of dengue virus.

We report here on an approach targeting the host reactive cysteinome to identify inhibitors of host factors required for the infectious cycle of Flaviviruses and other viruses. We used two parallel cellular phenotypic screens to identify a series of covalent inhibitors, exemplified by QL-XII-47, that are active against dengue virus. We show that the compounds effectively block viral protein expression and that this inhibition is associated with repression of downstream processes of the infectious cycle, and thus significantly contributes to the potent antiviral activity of these compounds.

Identification and Characterization of a Novel Broad-Spectrum Virus Entry Inhibitor.

Unlabelled: Virus entry into cells is a multistep process that often requires the subversion of subcellular machineries. A more complete understanding of these steps is necessary to develop new antiviral strategies. While studying the potential role of the actin network and one of its master regulators, the small GTPase Cdc42, during Junin virus (JUNV) entry, we serendipitously uncovered the small molecule ZCL278, reported to inhibit Cdc42 function as an entry inhibitor for JUNV and for vesicular stomatitis virus, lymphocytic choriomeningitis virus, and dengue virus but not for the nonenveloped poliovirus.

Lactimidomycin is a broad-spectrum inhibitor of dengue and other RNA viruses.

Dengue virus, a member of the Flaviviridae family, is a mosquito-borne pathogen and the causative agent of dengue fever. Despite the nearly 400 million new infections estimated annually, no vaccines or specific antiviral therapeutics are currently available. We identified lactimidomycin (LTM), a recently established inhibitor of translation elongation, as a potent inhibitor of dengue virus 2 infection in cell culture.

Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating device (NE2RD) for diagnostics.

Recent advances in biosensing technologies present great potential for medical diagnostics, thus improving clinical decisions. However, creating a label-free general sensing platform capable of detecting multiple biotargets in various clinical specimens over a wide dynamic range, without lengthy sample-processing steps, remains a considerable challenge. In practice, these barriers prevent broad applications in clinics and at patients' homes.

The bioactive lipid 4-hydroxyphenyl retinamide inhibits flavivirus replication.

Dengue virus (DENV), a member of the Flaviviridae family, is a mosquito-borne pathogen and the cause of dengue fever. The increasing prevalence of DENV worldwide heightens the need for an effective vaccine and specific antivirals. Due to the dependence of DENV upon the lipid biosynthetic machinery of the host cell, lipid signaling and metabolism present unique opportunities for inhibiting viral replication.

The encephalomyocarditis virus.

The encephalomyocarditis virus (EMCV) is a small non-enveloped single-strand RNA virus, the causative agent of not only myocarditis and encephalitis, but also neurological diseases, reproductive disorders and diabetes in many mammalian species. EMCV pathogenesis appears to be viral strain- and host-specific, and a better understanding of EMCV virulence factors is increasingly required. Indeed, EMCV is often used as a model for diabetes and viral myocarditis, and is also widely used in immunology as a double-stranded RNA stimulus in the study of Toll-like as well as cytosolic receptors.

Encephalomyocarditis virus 2A protein is required for viral pathogenesis and inhibition of apoptosis.

The encephalomyocarditis virus (EMCV), a Picornaviridae virus, has a wide host spectrum and can cause various diseases. EMCV virulence factors, however, are as yet ill defined. Here, we demonstrate that the EMCV 2A protein is essential for the pathogenesis of EMCV.

Three-dimensional vision based on a combination of gray-code and phase-shift light projection: analysis and compensation of the systematic errors.

A combination of phase-shift with gray-code light projection into a three-dimensional vision system based on the projection of structured light is presented. The gray-code method is exploited to detect without ambiguity even marked surface discontinuities, whereas the phase-shift technique allows the measurement of fine surface details. The system shows excellent linearity.

Low pressure pneumatic tourniquets: effectiveness at minimum recommended inflation pressures.

Complications from lower extremity pneumatic tourniquet use can range from transient to devastating. A major factor that can lead to complications is simply the applied site pressure. Recent advancements in tourniquet design, including increased width and curve allow for consistent hemostasis at pressures as low as 200 mm.