Zika virus (ZIKV), a mosquito-borne Flavivirus of international concern, causes congenital microcephaly in newborns and Guillain-Barré syndrome in adults. ZIKV capsid (C) protein, one of three key structural proteins, is essential for viral assembly and encapsidation. In dengue virus, a closely related flavivirus, the homologous C protein interacts with host lipid systems, namely intracellular lipid droplets, for successful viral replication.
View Article and Find Full Text PDFDengue virus (DENV) is a single-stranded (+)-sense RNA virus that infects humans and mosquitoes, posing a significant health risk in tropical and subtropical regions. Mature virions are composed of an icosahedral shell of envelope (E) and membrane (M) proteins circumscribing a lipid bilayer, which in turn contains a complex of the approximately 11 kb genomic RNA with capsid (C) proteins. Whereas the structure of the envelope is clearly defined, the structure of the packaged genome in complex with C proteins remains elusive.
View Article and Find Full Text PDFDengue, West Nile and Zika viruses are vector-borne flaviviruses responsible for numerous disease outbreaks in both Hemispheres. Despite relatively low mortality, infection may lead to potentially severe situations such as (depending on the virus): hypovolemic shock, encephalitis, acute flaccid paralysis, Guillain-Barré syndrome, congenital malformations (e.g.
View Article and Find Full Text PDFWiley Interdiscip Rev Nanomed Nanobiotechnol
November 2022
Infections caused by antibiotic-resistant bacteria continue to challenge the medical field, mostly due to conventional treatments inefficiency after years of overuse and misuse in clinics. Cases of multiresistant bacterial infections are increasing every year. This led the World Health Organization (WHO) to update the list of resistant micro-organisms that represent greatest threat to human health.
View Article and Find Full Text PDFThe circularization of viral genomes fulfills various functions, from evading host defense mechanisms to promoting specific replication and translation patterns supporting viral proliferation. Here, we describe the genomic structures and associated host factors important for flaviviruses genome circularization and summarize their functional roles. Flaviviruses are relatively small, single-stranded, positive-sense RNA viruses with genomes of approximately 11 kb in length.
View Article and Find Full Text PDFSuccess rates in drug discovery are extremely low, and the imbalance between new drugs entering clinical research and their approval is steadily widening. Among the causes of the failure of new therapeutic agents are the lack of safety and insufficient efficacy. On the other hand, timely disease diagnosis may enable an early management of the disease, generally leading to better and less costly outcomes.
View Article and Find Full Text PDFAlzheimer's disease (AD) is a neurodegenerative disorder that affects millions worldwide. Due to population ageing, the incidence of AD is increasing. AD patients develop cognitive decline and dementia, features for which is known, requiring permanent care.
View Article and Find Full Text PDFTrop Med Infect Dis
September 2020
Dengue virus (DENV), which can lead to fatal hemorrhagic fever, affects 390 million people worldwide. The closely related Zika virus (ZIKV) causes microcephaly in newborns and Guillain-Barré syndrome in adults. Both viruses are mostly transmitted by and mosquitoes, which, due to globalization of trade and travel alongside climate change, are spreading worldwide, paving the way to DENV and ZIKV transmission and the occurrence of new epidemics.
View Article and Find Full Text PDFDiabetes affects hundreds of millions of patients worldwide. Despite the advances in understanding the disease and therapeutic options, it remains a leading cause of death and of comorbidities globally. Islet amyloid polypeptide (IAPP), or amylin, is a hormone produced by pancreatic β-cells.
View Article and Find Full Text PDFIntrinsically disordered protein regions are at the core of biological processes and involved in key protein-ligand interactions. The Flavivirus proteins, of viruses of great biomedical importance such as Zika and dengue viruses, exemplify this. Several proteins of these viruses have disordered regions that are of the utmost importance for biological activity.
View Article and Find Full Text PDFDengue, West Nile and Zika, closely related viruses of the Flaviviridae family, are an increasing global threat, due to the expansion of their mosquito vectors. They present a very similar viral particle with an outer lipid bilayer containing two viral proteins and, within it, the nucleocapsid core. This core is composed by the viral RNA complexed with multiple copies of the capsid protein, a crucial structural protein that mediates not only viral assembly, but also encapsidation, by interacting with host lipid systems.
View Article and Find Full Text PDFFront Cell Infect Microbiol
December 2019
West Nile and dengue viruses are closely related flaviviruses, originating mosquito-borne viral infections for which there are no effective and specific treatments. Their capsid proteins sequence and structure are particularly similar, forming highly superimposable α-helical homodimers. Measuring protein-ligand interactions at the single-molecule level yields detailed information of biological and biomedical relevance.
View Article and Find Full Text PDFUnderstanding protein structure and dynamics, which govern key cellular processes, is crucial for basic and applied research. Intrinsically disordered protein (IDP) regions display multifunctionality via alternative transient conformations, being key players in disease mechanisms. IDP regions are abundant, namely in small viruses, allowing a large number of functions out of a small proteome.
View Article and Find Full Text PDFAim: γ' fibrinogen has been associated with thrombosis. Here the interactions between γ'γ' or γAγA fibrinogen and red blood cells (RBCs), and their role on fibrin clot properties were studied.
Materials & Methods: Atomic Force microscopy (AFM)-based force spectroscopy, rheological, electron and confocal microscopy, and computational approaches were conducted for both fibrinogen variants.
Lipid droplets (LDs) are intracellular organelles for neutral lipid storage, originated from the endoplasmic reticulum. They play an essential role in lipid metabolism and cellular homeostasis. In fact, LDs are complex organelles, involved in many more cellular processes than those initially proposed.
View Article and Find Full Text PDFα-Synuclein misfolding and aggregation is a hallmark in Parkinson's disease and in several other neurodegenerative diseases known as synucleinopathies. The toxic properties of α-synuclein are conserved from yeast to man, but the precise underpinnings of the cellular pathologies associated are still elusive, complicating the development of effective therapeutic strategies. Combining molecular genetics with target-based approaches, we established that glycation, an unavoidable age-associated post-translational modification, enhanced α-synuclein toxicity in vitro and in vivo, in Drosophila and in mice.
View Article and Find Full Text PDFWood industries and agricultural crops generate an inexhaustible supply of by-products like lignin, which constitutes an environmental problem. Increasing efforts have been done to find new applications for lignin. One of them is as a food additive, but its chemical nature makes it sensitive to browning which constitutes a major drawback for this type of lignin application.
View Article and Find Full Text PDFDengue virus (DENV) causes over 500,000 hospitalizations and 20,000 deaths worldwide every year. Dengue epidemics now reach temperate regions due to globalization of trade and travel and climate changes. Currently, there are no successful therapeutic or preventive approaches.
View Article and Find Full Text PDFDengue virus (DENV) infection affects millions of people and is becoming a major global disease for which there is no specific available treatment. pep14-23 is a recently designed peptide, based on a conserved segment of DENV capsid (C) protein. It inhibits the interaction of DENV C with host intracellular lipid droplets (LDs), which is crucial for viral replication.
View Article and Find Full Text PDFSelf-assembling amyloid-like peptides and proteins give rise to promising biomaterials with potential applications in many fields. Amyloid structures are formed by the process of molecular recognition and self-assembly, wherein a peptide or protein monomer spontaneously self-associates into dimers and oligomers and subsequently into supramolecular aggregates, finally resulting in condensed fibrils. Mature amyloid fibrils possess a quasi-crystalline structure featuring a characteristic fiber diffraction pattern and have well-defined properties, in contrast to many amorphous protein aggregates that arise when proteins misfold.
View Article and Find Full Text PDFPrion protein (PrP(C)) biosynthesis involves a multi-step process that includes translation and post-translational modifications. While PrP has been widely investigated, for the homolog Doppel (Dpl), limited knowledge is available. In this study, we focused on a vital step of eukaryotic protein biosynthesis: targeting by the signal recognition particle (SRP).
View Article and Find Full Text PDFUnlabelled: Dengue affects millions of people worldwide. No specific treatment is currently available, in part due to an incomplete understanding of the viral components' interactions with host cellular structures. We tested dengue virus (DENV) capsid protein (C) interaction with low- and very low-density lipoproteins (LDL and VLDL, respectively) using atomic force microscopy-based force spectroscopy, dynamic light scattering, NMR and computational analysis.
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