Biosynth’s Post

Biosynth have a new download available. Delve into the world of viruses in our new white paper brochure exploring the genetic makeup, infectious life cycle and the pathogenesis of the globally relevant dengue virus. https://lnkd.in/e_u5UY75 According to the European Centre for Disease Prevention and Control (ECDC), since the beginning of 2024 there have been 'over 5 million' cases of dengue fever and over '2,000 dengue-related deaths'. While numerous diagnostic tests for the dengue virus are currently on the market, there are few flavivirus panel assays and no specific dengue virus therapeutics available. Biosynth’s biologics division is leading the field in the development of target recombinant proteins and monoclonal antibodies for dengue fever. Our range of dengue virus proteins and antibodies provides global development teams and researchers with access to vital and new raw material to test samples, in the race to diagnose patients earlier and help with vaccine development. See our range of dengue virus catalog products which are also available for bulk and custom on request: https://lnkd.in/ebkp32BK #biologics #denguevirus #denguefever #viruses #diagnostics #ivd #vaccines #therapeutics #monoclonalantibodies #viralproteins #serology

#Molecular_Mechanism_In_The #Pathogenesis_Of_Dengue_Infection Dengue is the most rapidly emerging climate-sensitive infection, and there has been a 10-fold rise in cases over the past 20 years. Severe illness is characterized by vascular leakage, organ dysfunction, and severe bleeding which occur due to the direct effects of the viral non-structural protein NS1 and an aberrant host immune response. Dengue NS1 antigen, cytokines such as IL-1β, TNF-α, and IL-6, lipid mediators such as platelet-activating factor (PAF), leukotrienes and prostaglandins, VEGF, chymase, tryptase, and MMP-9 are thought to contribute to endothelial dysfunction. Many mechanisms contribute to liver dysfunction, including prolonged shock that causes hypoxic damage, direct liver cell death due to infection with the virus, and immune-mediated effects. Bleeding following dengue virus infection occurs due to multiple mechanisms including platelet activation by NS1, serotonin, and PAF, accompanied by a wide range of other coagulation abnormalities. #vaccine #dengue #infection #public_health

Happy to share our review on #dengue pathogenesis. We discuss the molecular mechanisms of dengue pathogenesis, the gaps in our knowledge, and recent advances, as well as the most crucial questions to be answered to enable the development of therapeutics, biomarkers, and vaccines. #ntds #vaccines #pathogenesis #virus #biomarkers #drugs #vascular leak https://lnkd.in/gXidfq7c

Our occupiers, The Native Antigen Company, are constantly developing new antigens and antibodies for emerging infectious diseases, allowing for novel vaccine & therapeutic research, and better diagnostics in pursuit of a safer world.   Did you know? They are known for a wide range of Virus-Like Particles (VLPs) consisting of structural proteins specific to the virus in question, presented as structurally accurate recombinant virions. VLPs are known to be highly immunogenic, and are non-infectious due to a lack of the core genetic material of the virus. Compared to single recombinant antigens, VLPs more effectively activate T-cell responses, usually generating higher titres of antibodies, allowing to capture and generate antibodies to epitopes spanning more than one protein's subunit.    Explore their comprehensive factsheet for a detailed list of virus-like particles here.👇 https://lnkd.in/emnMUCJg #antigens #antibodies #virus #lifescience

🌟 **In Silico Design of Drugs and Vaccines for Dengue Disease** 🌟 🔬 *Harnessing the power of computational modeling to fight dengue!* This study dives into two critical approaches for combatting dengue virus: drug discovery through the NS3 protease (NS3pro) enzyme and vaccine design targeting the E DENV protein. 🧬 **NS3 Protease Approach**: By using the crystal structures of the NS3pro enzyme from the Hepatitis C Virus (HCV) as a template, researchers are gaining crucial insights into the structure-function relationship of the dengue protease. This facilitates the design of substrate-based inhibitors for the dengue 2 virus. 💉 **E DENV Vaccine Design**: The in silico method is used to design dengue vaccines by leveraging the E DENV-2 and E DENV-3 proteins. These proteins act as backbones, providing immune responses against all four dengue virus serotypes. 📊 The study highlights how dengue drug design and vaccine development can benefit from computational tools, with the potential to revolutionize treatments in the near future. #DrugDiscovery #VaccineDesign #DengueResearch #Bioinformatics #InSilico #GlobalHealth

On March 24, in recognition of World tuberculosis (TB) Day, we highlight our efforts with AstraZeneca and National Institute of Allergy and Infectious Diseases (NIAID) in developing molecules for treating multidrug-resistant TB. Read more: https://lnkd.in/eJSWDHeP The first-line antituberculosis drug, isoniazid (INH), can treat TB by inhibiting the activity of the bacterial enzyme InhA. However, INH is only effective when it is activated by another bacterial enzyme, KatG. Multiple studies have shown that mutations in the katG gene is responsible for INH resistance. Discovery of InhA inhibitors that do not require KatG activation is therefore crucial to combat MDR TB. In this publication, we used DNA-encoded libraries of 100 billion unique molecules and identified multiple hit series that showed inhibition activity in cell-based assays through mechanisms that did not require KatG activation. The understanding would allow the development of next-generation compounds that are effective therapeutics to treat MDR TB. #YesWeCanEndTB #WorldTBDay #DrugDiscovery #DEL

To highlight the expression and purification of the recombinant dengue virus type-1 antigen exploiting the codon optimized full length envelope for increased yield in E. coli. Methods. A 6x His tag was inserted at the C terminus to facilitate purification. The purified protein was recognized in Western blot by Monoclonal antibody specific for the tag. The in vitro refolded recombinant protein was used to immunize ice for the development of hybridomas and also analyzed for its biological functionality with heparan sulfate binding assay. Results. The polyclonal anti-sera from the immunized mice were found to recognize the envelope protein thereby establishing the immunogenicity of the protein. Conclusion. The purified envelope protein could potentially be used towards dengue diagnostics and vaccine development efforts.

#editorchoice 📢 Discovery and Development Strategies for #SARSCoV2 NSP3 #Macrodomain Inhibitors 👨🎓 by Marion Schuller et al. 🔗 Full article: https://lnkd.in/gaYNftEJ The worldwide public health and socioeconomic consequences caused by the COVID-19 pandemic highlight the importance of increasing preparedness for viral disease outbreaks by providing rapid disease prevention and treatment strategies. The NSP3 macrodomain of coronaviruses including SARS-CoV-2 is among the viral protein repertoire that was identified as a potential target for the development of antiviral agents, due to its critical role in viral replication and consequent pathogenicity in the host. By combining virtual and biophysical screening efforts, we discovered several experimental small molecules and FDA-approved drugs as inhibitors of the NSP3 macrodomain. Analogue characterisation of the hit matter and crystallographic studies confirming binding modes, including that of the antibiotic compound aztreonam, to the active site of the macrodomain provide valuable structure–activity relationship information that support current approaches and open up new avenues for NSP3 macrodomain inhibitor development. 👉 This article belongs to the Special Issue: #ADPRibosylation in Pathogens https://lnkd.in/gjJ-SPmC

STILL PRE-CLINIC DATA... Researchers successfully generated soluble pentameric CTB-DV1EDIII with high yield using an E. coli expression system with the aid of our RNA-based chaperone (Chaperna) system. They confirmed the pentameric assembly and assessed the biological activity, including GM1 binding affinity, of CTB-DV1EDIII through size-exclusion chromatography (SEC), GM1 binding assays, and transmission electron microscopy (TEM). Furthermore, immunization of mice with CTB-DV1EDIII resulted in the induction of IgG2a antibodies. Sera from CTB-DV1EDIII-immunized mice exhibited higher neutralizing antibody titers when compared to sera from mice immunized with DV1EDIII or mCTB(Y12D)-DV1EDIII. Our study presents a highly soluble bacterial production platform for immune-enhanced dengue antigens achieved by fusing with CTB, serving as both a pentameric scaffold and built-in adjuvant.

An efficient plasmid-based system for the recovery of recombinant vesicular stomatitis virus encoding foreign glycoproteins. Abstract Viral glycoproteins mediate entry into host cells, thereby dictating host range and pathogenesis. In addition, they constitute the principal target of neutralizing antibody responses, making them important antigens in vaccine development. Recombinant vesicular stomatitis virus (VSV) encoding foreign glycoproteins can provide a convenient and safe surrogate system to interrogate the function, evolution, and antigenicity of viral glycoproteins from viruses that are difficult to manipulate or those requiring high biosafety level containment. However, the production of recombinant VSV can be technically challenging. In this work, we present an efficient and robust plasmid-based system for the production of recombinant VSV encoding foreign glycoproteins. We validate the system using glycoproteins from different viral families, including arenaviruses, coronaviruses, and hantaviruses, as well as highlight their utility for studying the effects of mutations on viral fitness. Overall, the methods described herein can facilitate the study of both native and recombinant VSV encoding foreign glycoproteins and can serve as the basis for the production of VSV-based vaccines. https://lnkd.in/ezTJScP3