Risultati finali Demonstrators, pilots, prototypes (8) A streamlined and efficient drug discovery testing cascade for CoVs A compound testing cascade to accelerate decision making for drug discovery Report on set up of the non-human primate model for SARS-CoV-2 infection and Report on set up of the non-human primate model for SARS-CoV-2 infection and diseaseease A report or publication that summarizes the development and clinical manifestations in the NHP model. The report also will summarize various primary and secondary endpoint that will facilitate evaluation of the test compounds. A HTS assay for the RTC under a 384 well plate format A HTS assay for the RTC under a 384-well plate format suitable to expedite focused screening of inhibitors (M6) and hit-to-lead efforts Harmonisation of SOP between WP6 partners and with WP1-7 SOP will be developed for prioritization of assets across various WPs, submitted and endorsed by the Steering Committee. Report on reverse genetics system Report should detail methods, development of mouse adapted virus based on reverse genetics and evaluation of the virus in a murine model establishing, primary and secondary endpoints in a non-trangenic strain. 1-CARE Small Molecule (SM) system impact model SM system conceptual impact model Report on setting up of rodent models A report to be written related to the rodent models to be used for testing of the 35 best candidates from WP1-4. 1. imported, characterised and bred K18 and humanised ACE-2 murine models in IVI and LUMC. 2. Characterised various Syrian Gold Hamster models in KU Leuven. Report should detail methods, controls used, primary and secondary endpoints and minimum results expected to show efficacy, as well as any processes to be used for PK/PD correlationsA report to be written related to the rodent models to be used for testing of the 35 best candidates from WP1-4. 1. imported, characterised and bred K18 and humanised ACE-2 murine models in IVI and LUMC. 2. Characterised various Syrian Gold Hamster models in KU Leuven] Report should detail methods, controls used, primary and secondary endpoints and minimum results expected to show efficacy, as well as any processes to be used for PK/PD correlations. Report on suitability of mouse adapted SARS-CoV-2 virus for lethal humanised ACE-2 model Report will detail methods and evaluation of the mouse model, dose used, primary and secondary endpoints and minimum results expected to show efficacy. Other (1) Analysis of targets for druggability AI-platforms will enable selection of a portfolio of tractable targets. Data from multiple databases, will be used to build predictive models for developability criteria e.g., potency, selectivity, ADME-Tox using diverse algorithms e.g., Random Forrest. Design objectives will drive the AI-design platform Documents, reports (7) 2-Portfolio report Update at Month 12 on progress to deliver optimised lead 4-Portfolio report Update at Month 24 on progress to deliver optimised lead Duo reporter HTS assay Validated HTS assay based on a reporter virus and reporter cell line 1-Portfolio report Update at Month 6 on progress to deliver optimised lead 3-Portfolio report Update at Month 18 on progress to deliver optimised lead Setup of the Clinical Trial Platform: Fast track process set up Setup of a Clinical Trial platform Fast track process is set up by M18 Setup of the Clinical Trial Platform: Implementation of representation concept completed Setup of a Clinical Trial Platform Implementation concept completed by M19 Open Research Data Pilot (1) Initial Data Management Plan An initial version of Data Management Plan will be prepared Pubblicazioni Peer reviewed articles (19) Humoral Responses Against Variants of Concern by COVID-19 mRNA Vaccines in Immunocompromised Patients. Autori: Obeid M, Suffiotti M, Pellaton C, et al. Pubblicato in: JAMA Oncol., Issue 8/5, 2022, Page(s) e220446, ISSN 2374-2445 Editore: American MEdical Association DOI: 10.1001/jamaoncol.2022.0446 Challenges related to data protection in clinical research before and during the COVID-19 pandemic: An exploratory study Autori: Lalova-Spinks T, De Sutter E, VAlcke P, Kindt E, Lejeune S, Negrouk A, Verhenneman G, Derèze JJ, Storme R, Borry P, Meszaros J, Huys I. Pubblicato in: Frontiers in Medicine, 2022, ISSN 2296-858X Editore: Frontiers Media S.A DOI: 10.3389/fmed.2022.995689 Changes in SARS-CoV-2 Spike versus Nucleoprotein Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies Autori: Craig Fenwick, Antony Croxatto, Alix T. Coste, Florence Pojer, Cyril André, Céline Pellaton, Alex Farina, Jérémy Campos, David Hacker, Kelvin Lau, Berend-Jan Bosch, Semira Gonseth Nussle, Murielle Bochud, Valerie D’Acremont, Didier Trono, Gilbert Greub, Giuseppe Pantaleo Pubblicato in: Journal of Virology, Issue 95/3, 2021, ISSN 0022-538X Editore: American Society for Microbiology DOI: 10.1128/jvi.01828-20 Patient-derived monoclonal antibody neutralizes SARS-CoV-2 Omicron variants and confers full protection in monkeys Autori: Craig Fenwick, Priscilla Turelli, Dongchun Ni, Laurent Perez, Kelvin Lau, Cécile Herate, Romain Marlin, Erica Lana, Céline Pellaton, Charlène Raclot, Line Esteves-Leuenberger, Jérémy Campos, Alex Farina, Flurin Fiscalini, Nathalie Dereuddre-Bosquet, Francis Relouzat, Rana Abdelnabi, Caroline S Foo, Johan Neyts, Pieter Leyssen, Yves Lévy, Florence Pojer, Henning Stahlberg, Roger LeGrand, Didi Pubblicato in: Nature Microbiology, Issue 20585276, 2022, Page(s) 1376-1389, ISSN 2058-5276 Editore: Nature Portfolio DOI: 10.1038/s41564-022-01198-6 Development and optimization of a high-throughput screening assay for in vitro anti-SARS-CoV-2 activity: Evaluation of 5676 Phase 1 Passed Structures Autori: Winston Chiu,Lore Verschueren,Christel Van den Eynde,Christophe Buyck,Sandra De Meyer,Dirk Jochmans,Denisa Bojkova,Sandra Ciesek,Jindrich Cinatl,Steven De Jonghe,Pieter Leyssen,Johan Neyts,Marnix Van Loock,Ellen Van Damme Pubblicato in: Journal of Medical Virology, Issue 94/7, 2022, Page(s) 3101-3111, ISSN 1096-9071 Editore: Wiley DOI: 10.1002/jmv.27683 A dual mechanism of action of AT-527 against SARS-CoV-2 polymerase Autori: Ashleigh Shannon, Véronique Fattorini, Bhawna Sama, Barbara Selisko, Mikael Feracci, Camille Falcou, Pierre Gauffre, Priscila El Kazzi, Adrien Delpal, Etienne Decroly, Karine Alvarez, Cécilia Eydoux, Jean-Claude Guillemot, Adel Moussa, Steven S. Good, Paolo La Colla, Kai Lin, Jean-Pierre Sommadossi, Yingxiao Zhu, Xiaodong Yan, Hui Shi, François Ferron & Bruno Canard Pubblicato in: Nature Communications, 2022, ISSN 2041-1723 Editore: Nature Publishing Group DOI: 10.1038/s41467-022-28113-1 A highly potent antibody effective against SARS-CoV-2 variants of concern Autori: Craig Fenwick, Priscilla Turelli, Laurent Perez, Céline Pellaton, Line Esteves-Leuenberger, Alex Farina, Jérémy Campos, Erica Lana, Flurin Fiscalini, Charlène Raclot, Florence Pojer, Kelvin Lau, Davide Demurtas, Marc Descatoire, Victor S. Joo, Mathilde Foglierini, Alessandra Noto, Rana Abdelnabi, Caroline S. Foo, Laura Vangeel, Johan Neyts, Wenjuan Du, Berend-Jan Bosch, Geertruida Veldman, Pie Pubblicato in: Cell Reports, 2021, Page(s) 109814, ISSN 2211-1247 Editore: Cell Press DOI: 10.1016/j.celrep.2021.109814 A high-throughput cell- and virus-free assay shows reduced neutralization of SARS-CoV-2 variants by COVID-19 convalescent plasma Autori: Craig Fenwick, Priscilla Turelli, Céline Pellaton, Alex Farina, Jérémy Campos, Charlène Raclot, Florence Pojer, Valeria Cagno, Semira Gonseth Nusslé, Valerie D’Acremont, Jan Fehr, Milo Puhan, Giuseppe Pantaleo, Didier Trono Pubblicato in: Science Translational Medicine, Issue 13/605, 2021, Page(s) eabi8452, ISSN 1946-6234 Editore: American Association for the Advancement of Science DOI: 10.1126/scitranslmed.abi8452 Rethinking informed consent in the time of COVID-19: An exploratory survey Autori: De Sutter E, Lalova-Spinks T, Borry P, Valcke P, Kindt E, Negrouk A, Verhenneman G, Derèze JJ, Storme R, Huys I Pubblicato in: Frontiers in Medicine, 2022, ISSN 2296-858X Editore: Frontiers Media S.A DOI: 10.3389/fmed.2022.995688 Computed tomography and [18F]-FDG PET imaging provide additional readouts for COVID-19pathogenesis and therapies evaluation in non-human primates Autori: Thibaut Naninck, Nidhal Kahlaoui, Julien Lemaitre, Pauline Maisonnasse, Antoine De Mori, Quentin Pascal, Vanessa Contreras, Romain Marlin, Francis Relouzat, Benoıt Delache, Cecile Herate, Yoann Aldon, Marit van Gils, Nerea Zabaleta, Raphael Ho Tsong Fang, Nathalie Bosquet, Rogier W. Sanders, Luk H. Vandenberghe, Catherine Chapon, and Roger Le Grand Pubblicato in: IScience, Issue 25/4, 2022, Page(s) 104101, ISSN 2589-0042 Editore: Cell Press, Elsevier DOI: 10.1016/j.isci.2022.104101 Design, immunogenicity, and efficacy of a pan-sarbecovirus dendritic-cell targeting vaccine Autori: Séverin Coléon, Aurélie Wiedemann, Mathieu Surénaud, Christine Lacabaratz, Sophie Hue, Mélanie Prague, Minerva Cervantes-Gonzalez, Zhiqing Wang, Jerome Ellis, Amandine Sansoni, Camille Pierini, Quentin Bardin, Manon Fabregue, Sarah Sharkaoui, Philippe Hoest, Léa Dupaty, Florence Picard, Marwa El Hajj, Mireille Centlivre, Jade Ghosn, French COVID Cohort Study Group, Rodolphe Thiébaut, Sylvai Pubblicato in: EBioMedicine, Issue 80, 2022, Page(s) 104062, ISSN 2352-3964 Editore: Elsevier BV DOI: 10.1016/j.ebiom.2022.104062 CD177, a specific marker of neutrophil activation, is associated with coronavirus disease 2019 severity and death Autori: Yves Lévy, Aurélie Wiedemann, Boris P. Hejblum, Mélany Durand, Cécile Lefebvre, Mathieu Surénaud, Christine Lacabaratz, Matthieu Perreau, Emile Foucat, Marie Déchenaud, Pascaline Tisserand, Fabiola Blengio, Benjamin Hivert, Marine Gauthier, Minerva Cervantes-Gonzalez, Delphine Bachelet, Cédric Laouénan, Lila Bouadma, Jean-François Timsit, Yazdan Yazdanpanah, Giuseppe Pantaleo, Hakim Hocin Pubblicato in: iScience, Issue 24/7, 2021, Page(s) 102711, ISSN 2589-0042 Editore: Cell Press Elsevier Inc. DOI: 10.1016/j.isci.2021.102711 Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern Autori: Vangeel L, Chiu W, De Jonghe S, Maes P, Slechten B, Raymenants J, Andre E, Leyssen P, Neyts J and Jochmans D. Pubblicato in: Antiviral Research, Issue 198, 2022, Page(s) 105252, ISSN 0166-3542 Editore: Elsevier BV DOI: 10.1016/j.antiviral.2022.105252 Generation of a VeroE6 Pgp gene knock out cell line and its use in SARS-CoV-2 antiviral study Autori: Yuao Zhu, Joe Binder, Irina Yurgelonis, Devendra K Rai, Sarah Lazarro, Chester Costales, Keith Kobylarz, Patricia McMonagle, Claire M Steppan, Lisa Aschenbrenner, Annaliesa S Anderson, Rhonda D Cardin Pubblicato in: Antiviral Research, 2022, ISSN 0166-3542 Editore: Elsevier BV DOI: 10.1016/j.antiviral.2022.105429 Refolding of lid subdomain of SARS-CoV-2 nsp14 upon nsp10 interaction releases exonuclease activity Autori: Anna Czarna, Jacek Plewska, Leanid Kresik, Alex Matsuda, Abdulkarim Karim, Colin Robinson, Sean O'Byrne, Fraser Cunningham, Irene Georgiou, Piotr Wilk, Magdalena PAchota, Grzegorz Popowicz, Paul Graham Wyatt, Grzegorz Dublin, Krzystof Pyrc. Pubblicato in: Structure, Issue 09692126, 2022, Page(s) 1050-1054, ISSN 0969-2126 Editore: Cell Press DOI: 10.1016/j.str.2022.04.014 Lack of Evidence of Angiotensin-Converting Enzyme 2 Expression and Replicative Infection by SARS-CoV-2 in Human Endothelial Cells Autori: Ian R. McCracken, Gaye Saginc, Liqun He, Alik Huseynov, Alison Daniels, Sarah Fletcher, Claire Peghaire, Viktoria Kalna, Maarja Andaloussi-Mäe, Lars Muhl, Nicky M. Craig, Samantha J. Griffiths, Jürgen G. Haas, Christine Tait-Burkard, Urban Lendahl, Graeme M. Birdsey, Christer Betsholtz, Michela Noseda, Andrew H. Baker, Anna M. Randi Pubblicato in: Circulation, Issue 143/8, 2021, Page(s) 865-868, ISSN 0009-7322 Editore: Lippincott Williams & Wilkins Ltd. DOI: 10.1161/circulationaha.120.052824 Synthesis, Structure–Activity Relationships, and Antiviral Profiling of 1-Heteroaryl-2-Alkoxyphenyl Analogs As Inhibitors of SARS-CoV-2 Replication. Autori: Dorothée Bardiot, Laura Vangeel, Mohamed Koukni, Philippe Arzel, Marleen Zwaagstra, Heyrhyoung Lyoo, Patrick Wanninge,n Shamshad Ahmad, Linlin Zhang, Xinyuanyuan Sun, Adrien Delpal, Cecilia Eydoux, Jean-Claude Guillemot, Eveline Lescrinier, Hugo Klaassen, Pieter Leyssen, Dirk Jochmans, Karolien Castermans, Rolf Hilgenfeld, Colin Robinso,n Etienne Decroly, Bruno Canard, Eric Snijder, Martijn Hemer Pubblicato in: Molecules, Issue 27/3, 2022, Page(s) 1052, ISSN 1420-3049 Editore: Multidisciplinary Digital Publishing Institute (MDPI) DOI: 10.3390/molecules27031052 Shape-Restrained Modeling of Protein–Small-Molecule Complexes with High Ambiguity Driven DOCKing Autori: Panagiotis I. Koukos, Manon Réau, Alexandre M. J. J. Bonvin Pubblicato in: Journal of Chemical Information and Modeling, Issue 61/9, 2021, Page(s) 4807-4818, ISSN 1549-9596 Editore: American Chemical Society DOI: 10.1021/acs.jcim.1c00796 Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates Autori: Pauline Maisonnasse, Jérémie Guedj, Vanessa Contreras, Sylvie Behillil, Caroline Solas, Romain Marlin, Thibaut Naninck, Andres Pizzorno, Julien Lemaitre, Antonio Gonçalves, Nidhal Kahlaoui, Olivier Terrier, Raphael Ho Tsong Fang, Vincent Enouf, Nathalie Dereuddre-Bosquet, Angela Brisebarre, Franck Touret, Catherine Chapon, Bruno Hoen, Bruno Lina, Manuel Rosa Calatrava, Sylvie van der Werf, Xavi Pubblicato in: Nature, Issue 585/7826, 2020, Page(s) 584-587, ISSN 0028-0836 Editore: Nature Publishing Group DOI: 10.1038/s41586-020-2558-4 Other (1) High Throughput cryo-EM epitope mapping of SARS-CoV-2 spike protein antibodies using EPU multigrid Autori: Ieva Drulyte, Stefan Koester, Dianna Lundberg, Kurt Eng, Andrey Malyutin, Aaron McGrath, Chunyan Wang, Frank van Kuppeveld, Berend-Jan Bosch, Mazdak Radjainia, Jerry Thomas, Maureen Magnay and Daniel Hurdiss Pubblicato in: 2022 Editore: ThermoFischer È in corso la ricerca di dati su OpenAIRE... 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