Publications by authors named "Eberle R"

Article Synopsis
  • The study investigates the use of electroretinography (ERG) as a potential measure of neurodegeneration in people with multiple sclerosis (pwMS) with more advanced disease.
  • Delays in ERG peak times were found in pwMS regardless of previous optic neuritis, indicating common bipolar dysfunction, but no influence from EDSS scores or disease status was observed.
  • While ERG shows abnormal findings in pwMS with moderate to severe disability, it may not be effective for monitoring disease progression or prognosis.
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Over a century has passed since Alois Alzheimer first described Alzheimer's disease (AD), and since then, researchers have made significant strides in understanding its pathology. One key feature of AD is the presence of amyloid-β (Aβ) peptides, which form amyloid plaques, and therefore, it is a primary target for treatment studies. Naturally occurring peptides have garnered attention for their potential pharmacological benefits, particularly in the central nervous system.

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  • TMPRSS2 is an accessory protease that increases the entry of SARS-CoV-2 into cells expressing ACE2, impacting how the virus interacts with host cells during infection.
  • Experiments showed that TMPRSS2 enhances the internalization of the virus, improves early replication rates, and modifies immune responses, depending on the virus variant.
  • The study reveals that TMPRSS2 not only affects viral uptake and replication but also leads to increased cell death and drives the evolution of viral mutations, linking these processes to the effectiveness of the host's immune response.
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Oropouche virus (OROV) is a member of the family and the causative agent of a dengue-like febrile illness transmitted by mosquitoes. Although mild symptoms generally occur, complications such as encephalitis and meningitis may develop. A lack of proper diagnosis, makes it a potential candidate for new epidemics and outbreaks like other known arboviruses such as Dengue, Yellow Fever and Zika virus.

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The arbovirus Chikungunya (CHIKV) is transmitted by mosquitoes in urban environments, and in humans, it triggers debilitating symptoms involving long-term complications, including arthritis and Guillain-Barré syndrome. The development of antiviral therapies is relevant, as no efficacious vaccine or drug has yet been approved for clinical application. As a detailed map of molecules underlying the viral infection can be obtained from the metabolome, we validated the metabolic signatures of Vero E6 cells prior to infection (CC), following CHIKV infection (CV) and also upon the inclusion of the nsP2 protease inhibitor wedelolactone (CWV), a coumestan which inhibits viral replication processes.

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Oropouche virus (OROV) is an emerging vector-borne arbovirus found in South America that causes Oropouche fever, a febrile infection similar to dengue fever. It has a high epidemic potential, causing illness in over 500,000 cases diagnosed since the virus was first discovered in 1955. Currently, the prevention of human viral infection depends on vaccination, but availability for many viruses is limited, and they are classified as neglected viruses.

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The primary function of virus proteases is the proteolytic processing of the viral polyprotein. These enzymes can also cleave host cell proteins, which is important for viral pathogenicity, modulation of cellular processes, viral replication, the defeat of antiviral responses and modulation of the immune response. It is known that COVID-19 can influence multiple tissues or organs and that infection can damage the functionality of the brain in multiple ways.

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Arboviruses such as Dengue, yellow fever, West Nile, and Zika are flaviviruses vector-borne RNA viruses transmitted biologically among vertebrate hosts by blood-taking vectors. Many flaviviruses are associated with neurological, viscerotropic, and hemorrhagic diseases, posing significant health and socioeconomic concerns as they adapt to new environments. Licensed drugs against them are currently unavailable, so searching for effective antiviral molecules is still necessary.

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During the replication process of SARS-CoV-2, the main protease of the virus [3-chymotrypsin-like protease (3CL)] plays a pivotal role and is essential for the life cycle of the pathogen. Numerous studies have been conducted so far, which have confirmed 3CL as an attractive drug target to combat COVID-19. We describe a novel and efficient next-generation sequencing (NGS) supported phage display selection strategy for the identification of a set of SARS-CoV-2 3CL targeting peptide ligands that inhibit the 3CL protease, in a competitive or noncompetitive mode, in the low μM range.

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Confining compartments are ubiquitous in biology, but there have been few experimental studies on the thermodynamics of protein folding in such environments. Recently, we reported that the stability of a model protein substrate in the GroEL/ES chaperonin cage is reduced dramatically by more than 5 kcal mol compared to that in bulk solution, but the origin of this effect remained unclear. Here, we show that this destabilization is caused, at least in part, by a diminished hydrophobic effect in the GroEL/ES cavity.

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Since the intricate and complex steps in pathogenesis and host-viral interactions of arthropod-borne viruses or arboviruses are not completely understood, the multi-omics approaches, which encompass proteomics, transcriptomics, genomics and metabolomics network analysis, are of great importance. We have reviewed the omics studies on mosquito-borne viruses of the , and families, specifically for Chikungunya, Mayaro, Oropouche and Rift Valley Fever viruses. Omics studies can potentially provide a new perspective on the pathophysiology of arboviruses, contributing to a better comprehension of these diseases and their effects and, hence, provide novel insights for the development of new antiviral drugs or therapies.

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Background & Aims: Hepatitis B virus (HBV) was identified as an enveloped DNA virus with a diameter of 42 nm. Multivesicular bodies play a central role in HBV egress and exosome biogenesis. In light of this, it was studied whether intact virions wrapped in exosomes are released by HBV-producing cells.

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Viruses of the giant virus family are characterized by a structurally conserved scaffold-capsid protein that shapes the icosahedral virion. The vaccinia virus (VACV) scaffold protein D13, however, transiently shapes the newly assembled viral membrane in to a sphere and is absent from the mature brick-shaped virion. In infected cells D13, a 62 kDa polypeptide, forms trimers that arrange in hexamers and a honey-comb like lattice.

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Several neurotropic viruses are members of the flavivirus and alphavirus families. Infections caused by these viruses may cause long-term neurological sequelae in humans. The continuous emergence of infections caused by viruses around the world, such as the chikungunya virus (CHIKV) (Alphavirus genus), the zika virus (ZIKV) and the yellow fever virus (YFV) (both of the Flavivirus genus), warrants the development of new strategies to combat them.

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The C30 endopeptidase (3C-like protease; 3CL) is essential for the life cycle of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) since it plays a pivotal role in viral replication and transcription and, hence, is a promising drug target. Molecules isolated from animals, insects, plants, or microorganisms can serve as a scaffold for the design of novel biopharmaceutical products. Crotamine, a small cationic peptide from the venom of the rattlesnake , has been the focus of many studies since it exhibits activities such as analgesic, in vitro antibacterial, and hemolytic activities.

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Article Synopsis
  • The SARS-CoV-2 main protease (3CL) is crucial for viral replication by cleaving polyproteins into essential nonstructural proteins, making it a key target for drug development against Covid-19.
  • Numerous inhibitors have been identified, but D-peptides, which offer advantages over traditional L-peptides, have not been thoroughly explored as treatment options for 3CL.
  • This study introduces a computational approach using structure-based virtual screening to discover D-peptides that inhibit 3CL, demonstrating significant inhibitory effects from selected D-tetrapeptides and showcasing the method's potential for broader applications in protein inhibition.
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Arboviruses are transmitted by arthropods (arthropod-borne virus) which can be mosquitoes or other hematophagous arthropods, in which their life cycle occurs before transmission to other hosts. Arboviruses such as Dengue, Zika, Saint Louis Encephalitis, West Nile, Yellow Fever, Japanese Encephalitis, Rocio and Murray Valley Encephalitis viruses are some of the arboviruses transmitted biologically among vertebrate hosts by blood-taking vectors, mainly Aedes and Culex sp., and are associated with neurological, viscerotropic, and hemorrhagic reemerging diseases, posing as significant health and socioeconomic concern, as they become more and more adaptive to new environments, to arthropods vectors and human hosts.

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Article Synopsis
  • Hesperidin and Hesperetin, flavanones found in citrus fruits, have demonstrated antiviral properties against arboviruses like Dengue, Yellow Fever, and West Nile Virus.
  • Both compounds inhibit the NS2B/NS3 proteases of these viruses noncompetitively, with Hesperidin showing an IC value under 5 µM and Hesperetin under 70 µM.
  • The study suggests that these flavonoids can be optimized for developing new anti-flavivirus medications due to their effective dissociation constants well below 30 µM.
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Since the first report of a new pneumonia disease in December 2019 (Wuhan, China) the WHO reported more than 148 million confirmed cases and 3.1 million losses globally up to now. The causative agent of COVID-19 (SARS-CoV-2) has spread worldwide, resulting in a pandemic of unprecedented magnitude.

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Article Synopsis
  • Current studies on COVID-19 focus on targeting the main protease enzyme (3CL) of SARS-CoV-2, which is essential for the virus's replication.
  • Researchers used molecular dynamics simulations to analyze around 150 compounds that previously showed potential for binding to 3CL, aiming to refine and identify effective inhibitors.
  • Among the promising compounds, corilagin and lurasidone showed significant activity against the enzyme, indicating potential for drug repurposing, while testosterone also exhibited moderate inhibitory effects, potentially explaining the higher severity of COVID-19 in older men.
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The potential outcome of flavivirus and alphavirus co-infections is worrisome due to the development of severe diseases. Hundreds of millions of people worldwide live under the risk of infections caused by viruses like chikungunya virus (CHIKV, genus Alphavirus), dengue virus (DENV, genus Flavivirus), and zika virus (ZIKV, genus Flavivirus). So far, neither any drug exists against the infection by a single virus, nor against co-infection.

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Aging of the immune system is characterized by the loss of naïve T-cells, increased inflammation, and immune function impairment. Chronic infection with cytomegalovirus is thought to play a role in age-related changes in immunity. Therefore, to assess the effect of pathogens such as cytomegalovirus on the immune system, we determined lymphocyte populations and inflammatory markers over a 3-y period in captive, middle-age baboons, with various exposure to pathogens and shedding pressure.

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is a pathogenic bacterium with great veterinary and economic importance. It is classified into two biovars: , nitrate-negative, that causes lymphadenitis in small ruminants and , nitrate-positive, causing ulcerative lymphangitis in equines. With the explosive growth of available genomes of several strains, pan-genome analysis has opened new opportunities for understanding the dynamics and evolution of .

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Background: To date, several cases of transfusion-transmitted ZIKV infections have been confirmed. Multiple studies detected prolonged occurrence of ZIKV viral RNA in whole blood as compared to plasma samples indicating potential ZIKV interaction with hematopoietic cells. Also, infection of cells from the granulocyte/macrophage lineage has been demonstrated.

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Zoonotic monkey B virus ( 1; BV) infections are extremely serious and usually fatal. Drugs currently used for treatment were developed for the treatment of herpes simplex virus but are less effective against BV. Effective suppression of viral replication in the skin could prevent the virus from invading the nervous system.

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