The Importance of Biobanking for Response to Pandemics Caused by Emerging Viruses:The European Virus Archive As an Observatory of the Global Response to the Zika Virus and COVID-19 Crisis

When a new virus emerges and causes a significant epidemic, the emergency response relies on diagnostics, surveillance, testing, and proposal of treatments if they exist, and also in the longer term, redirection of research efforts toward understanding the newly discovered pathogen. To serve these goals, viral biobanks play a crucial role. The European Virus Archive (EVA) is a network of biobanks from research laboratories worldwide that has combined into a common set of practices and mutually beneficial objectives to give scientists the tools that they need to study viruses in general, and also to respond to a pandemic caused by emerging viruses. Taking the most recent outbreaks of the Zika virus and SARS-CoV-2 as examples, by looking at who orders what and when to the EVA, we illustrate how the global science community at large, public health, fundamental research and private companies, reorganize their activity toward diagnosing, understanding, and fighting the new pathogen.</p

Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

BackgroundThe ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur.AimWe aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available.MethodsHere we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology.ResultsThe workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive - Global (EVAg), a European Union infrastructure project.ConclusionThe present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks

Fonctionnalité, activation, régulation allostérique des caspases, les effecteurs de l'apoptose (création de nouveaux inhibiteurs de caspases)

Depuis sa découverte, l'apoptose, ou mort cellulaire programmée, a suscité un intérêt croissant de la part de la communauté scientifique internationale. Suivant un stimulus, le signal apoptotique est transmis et amplifié au sein de la cellule par une famille de protéases à cystéine appelée caspase. L'implication de l'apoptose dans un grand nombre de maladies humaines en a fait un sujet de recherche majeur. L'objectif de cette thèse de recherche est d'étudier les caspases, dans le but de créer une nouvelle génération de molécules thérapeutiques. Chaque caspase reconnaît spécifiquement une séquence tetrapeptidique donnée. Les divergences entre les sites actifs des différentes caspases reflètent leur sélectivité de substrat. A partir des structures tridimensionnelles de 4 caspases, les modèles structuraux de 7 autres caspases ont été créés. L'utilisation de paires d'inhibiteurs tetrapeptidiques a permis d'effectuer une étude fonctionnelle approfondie de chaque sous-site composant le site actif des caspases. Le lien entre ces analyses structurelle et fonctionnelle a mis en évidence les principales caractéristiques des sites actifs des caspases et devrait permettre d'améliorer le développement d'inhibiteurs compétitifs plus sélectifs. Le mécanisme d'activation des caspases sera également discuté. Finalement, l'identification d'un site de fixation des nucléotides dans caspase-9 sera traité. Cette enzyme est activée par sa fixation à Apaf-1, formant un complexe protéique appelé apoptosome. Ce site de fixation serait impliqué dans l'inhibition de l'activité de l'apoptosome par les nucléotides. L'implication au niveau cellulaire de ce phénomène sera discutée en détail ainsi que l'éventuelle utilisation d'analogues de nucléotides à des fins thérapeutiques. La concentration en nucléotides jouerait un rôle majeur dans la régulation de l'apoptose.AIX-MARSEILLE1-BU Sci.St Charles (130552104) / SudocSudocFranceF

An RNA cap (nucleoside-2′-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization

Viruses represent an attractive system with which to study the molecular basis of mRNA capping and its relation to the RNA transcription machinery. The RNA-dependent RNA polymerase NS5 of flaviviruses presents a characteristic motif of S-adenosyl-l-methionine-dependent methyltransferases at its N-terminus, and polymerase motifs at its C-terminus. The crystal structure of an N-terminal fragment of Dengue virus type 2 NS5 is reported at 2.4 Å resolution. We show that this NS5 domain includes a typical methyltransferase core and exhibits a (nucleoside-2′-O-)-methyltransferase activity on capped RNA. The structure of a ternary complex comprising S-adenosyl-l-homocysteine and a guanosine triphosphate (GTP) analogue shows that 54 amino acids N-terminal to the core provide a novel GTP-binding site that selects guanine using a previously unreported mechanism. Binding studies using GTP- and RNA cap-analogues, as well as the spatial arrangement of the methyltransferase active site relative to the GTP-binding site, suggest that the latter is a specific cap-binding site. As RNA capping is an essential viral function, these results provide a structural basis for the rational design of drugs against the emerging flaviviruses

The Importance of Biobanking for Response to Pandemics Caused by Emerging Viruses: The European Virus Archive As an Observatory of the Global Response to the Zika Virus and COVID-19 Crisis

When a new virus emerges and causes a significant epidemic, the emergency response relies on diagnostics, surveillance, testing, and proposal of treatments if they exist, and also in the longer term, redirection of research efforts toward understanding the newly discovered pathogen. To serve these goals, viral biobanks play a crucial role. The European Virus Archive (EVA) is a network of biobanks from research laboratories worldwide that has combined into a common set of practices and mutually beneficial objectives to give scientists the tools that they need to study viruses in general, and also to respond to a pandemic caused by emerging viruses. Taking the most recent outbreaks of the Zika virus and SARS-CoV-2 as examples, by looking at who orders what and when to the EVA, we illustrate how the global science community at large, public health, fundamental research and private companies, reorganize their activity toward diagnosing, understanding, and fighting the new pathogen

Access and benefit-sharing by the European Virus Archive in response to COVID-19

Erratum in Correction to Lancet Microbe 2021; published online Nov 16. https://doi.org/10.1016/S2666-5247(21)00211-1. [No authors listed] Lancet Microbe. 2022 Jan;3(1):e8. doi: 10.1016/S2666-5247(21)00325-6. Epub 2021 Nov 26. PMID: 34870252 Free PMC article.International audienceBiobanking infrastructures, which are crucial for responding early to new viral outbreaks, share pathogen genetic resources in an affordable, safe, and impartial manner and can provide expertise to address access and benefit-sharing issues. The European Virus Archive has had a crucial role in the global response to the COVID-19 pandemic by distributing EU-subsidised (free of charge) viral resources to users worldwide, providing non-monetary benefit sharing, implementing access and benefit-sharing compliance, and raising access and benefit-sharing awareness among members and users. All currently available SARS-CoV-2 material in the European Virus Archive catalogue, including variants of concern, are not access and benefit-sharing cases per se, but multilateral benefit-sharing has nevertheless occurred. We propose and discuss how a multilateral system enabling access and benefit-sharing from pathogen genetic resources, based on the European Virus Archive operational model, could help bridge the discrepancies between the current bilateral legal framework for pathogen genetic resources and actual pandemic response practices

Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

Background: The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. Aim: We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. Methods: Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. Results: The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive - Global (EVAg), a European Union infrastructure project. Conclusion: The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks