Search results for "Zika virus"

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…

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…

Zika virus. A teratogenic agent for the eyes

2017

Novel activities of safe-in-human broad-spectrum antiviral agents

2018

According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-in-human antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley feve…

Linking Only Aedes aegypti with Zika Virus Has World-Wide Public Health Implications

2017

Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins

2017

Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensiti…

Prevalence of microcephaly in Europe: population based study.

2016

Objectives: Microcephaly is a congenital anomaly where the baby’s head is smaller than expected when compared with babies of the same sex, age and ethnicity. Many of these babies will have underdeveloped brains. This study aimed to provide contemporary estimates of the prevalence of microcephaly in Europe, determine if the diagnosis of microcephaly is consistent across Europe and to evaluate whether changes in prevalence would be detected using the current European surveillance performed by EUROCAT (the European Surveillance of Congenital Anomalies). Design: A questionnaire and a population-based, observational study Setting: 24 EUROCAT registries covering 570,000 births annually in 15 coun…

Real-time parameter estimation of Zika outbreaks using model averaging

2017

SUMMARYEarly prediction of the final size of any epidemic and in particular for Zika disease outbreaks can be useful for health authorities in order to plan the response to the outbreak. The Richards model is often been used to estimate epidemiological parameters for arboviral diseases based on the reported cumulative cases in single- and multi-wave outbreaks. However, other non-linear models can also fit the data as well. Typically, one follows the so called post selection estimation procedure, i.e., selects the best fitting model out of the set of candidate models and ignores the model uncertainty in both estimation and inference since these procedures are based on a single model. In this…

The Medicinal Chemistry of Zika Virus

2021

Arthropod-borne viruses, also known as arboviruses, are transmitted by bites of infected mosquito or tick vectors. In this context, the Flavivirus genus is mainly transmitted by mosquitoes from the Aedes genus, being the Ae. africanus, Ae. aegypti, and Ae. Albopictus species are responsible for transmitting the Zika virus (ZIKV). It is a lipid-enveloped virus constitute of an RNA genome, which is translated into a polyprotein encoding three structural proteins {(capsid (C), membrane (M), and envelope (E)} and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). Several biological targets have been identified for developing antiviral agents against ZIKV, which could pre…

Joint Estimation of Relative Risk for Dengue and Zika Infections, Colombia, 2015–2016

2019

We jointly estimated relative risk for dengue and Zika virus disease (Zika) in Colombia, establishing the spatial association between them at the department and city levels for October 2015–December 2016. Cases of dengue and Zika were allocated to the 87 municipalities of 1 department and the 293 census sections of 1 city in Colombia. We fitted 8 hierarchical Bayesian Poisson joint models of relative risk for dengue and Zika, including area- and disease-specific random effects accounting for several spatial patterns of disease risk (clustered or uncorrelated heterogeneity) within and between both diseases. Most of the dengue and Zika high-risk municipalities varied in their risk distributio…