Corona Accelerated R&D in Europe

Livrables

A streamlined and efficient drug discovery testing cascade for CoVs

A compound testing cascade to accelerate decision making for drug discovery

Emergency/Preparedness set of molecules for WP2

A toolbox with at least 8 assays able to measure binding and/or activity of the targeted proteins listed in task 2.6

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.

Coordinated AI-platform

Drive efficient compound designs for phenotypic and target-based programs

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

Mid-term data Management Plan

Data management plan mid-term version at Month 36

Initial Data Management Plan

An initial version of Data Management Plan will be prepared

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

Publications

A SCID Mouse Model To Evaluate the Efficacy of Antivirals against SARS-CoV-2 Infection

Auteurs: Abdelnabi R, Foo CS, Kaptein SJF, Boudewijns R, Vangeel L, de Jonghe S, Jocmans D, Weynand B, Neyts J.
Publié dans: Journal of virology, 2022, ISSN 0022-538x
Éditeur: American Society for Microbiology
DOI: 10.1128/jvi.00758-22

Humoral Responses Against Variants of Concern by COVID-19 mRNA Vaccines in Immunocompromised Patients.

Auteurs: Obeid M, Suffiotti M, Pellaton C, et al.
Publié dans: JAMA Oncol., Numéro 8/5, 2022, Page(s) e220446, ISSN 2374-2445
Éditeur: American MEdical Association
DOI: 10.1001/jamaoncol.2022.0446

A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein

Auteurs: Vito Thijssen, Daniel L Hurdiss , Oliver J Debski-Antoniak, Matthew A Spence, Charlotte Franck, Alexander Norman, Anupriya Aggarwal, Nadia J Mokiem, David A A van Dongen, Stein W Vermeir, Minglong Liu, Wentao Li, Marianthi Chatziandreou, Tim Donselaar, Wenjuan Du, Ieva Drulyte, Berend-Jan Bosch, Joost Snijder, Stuart G Turville, Richard J Payne, Colin J Jackson, Frank J M van Kuppeveld, Seino A K
Publié dans: PNAS, 2023, ISSN 0027-8424
Éditeur: National Academy of Sciences
DOI: 10.1073/pnas.2303292120

Auteurs: 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.
Publié dans: Frontiers in Medicine, 2022, ISSN 2296-858X
Éditeur: 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

Auteurs: 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
Publié dans: Journal of Virology, Numéro 95/3, 2021, ISSN 0022-538X
Éditeur: 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

Auteurs: 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
Publié dans: Nature Microbiology, Numéro 20585276, 2022, Page(s) 1376-1389, ISSN 2058-5276
Éditeur: 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

Auteurs: 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
Publié dans: Journal of Medical Virology, Numéro 94/7, 2022, Page(s) 3101-3111, ISSN 1096-9071
Éditeur: Wiley
DOI: 10.1002/jmv.27683

A dual mechanism of action of AT-527 against SARS-CoV-2 polymerase

Auteurs: 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
Publié dans: Nature Communications, 2022, ISSN 2041-1723
Éditeur: Nature Publishing Group
DOI: 10.1038/s41467-022-28113-1

A highly potent antibody effective against SARS-CoV-2 variants of concern

Auteurs: 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
Publié dans: Cell Reports, 2021, Page(s) 109814, ISSN 2211-1247
Éditeur: Cell Press
DOI: 10.1016/j.celrep.2021.109814

Identification of Z-Tyr-Ala-CHN2, a Cathepsin L Inhibitor with Broad-Spectrum Cell-Specific Activity against Coronaviruses, including SARS-CoV-2

Auteurs: Doijen J, Temmerman K, Van der Eynde C, Diels A, Van der Broeck N, Van Gool M, Heo I, Jaensch S, Zwaagstra M, Diosa Toro M, Chiu W, de Jonghe S, Leyssen P, Bojkova D, Ciesek S, Cinati J, Verschueren L, Buyck C, Van Kupeveld F, Neyts J, Van Loock M, Van DAmme E.
Publié dans: Microorganisms, 2023, ISSN 2076-2607
Éditeur: MDPI
DOI: 10.3390/microorganisms11030717

A high-throughput cell- and virus-free assay shows reduced neutralization of SARS-CoV-2 variants by COVID-19 convalescent plasma

Auteurs: 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
Publié dans: Science Translational Medicine, Numéro 13/605, 2021, Page(s) eabi8452, ISSN 1946-6234
Éditeur: American Association for the Advancement of Science
DOI: 10.1126/scitranslmed.abi8452

Rethinking informed consent in the time of COVID-19: An exploratory survey

Auteurs: De Sutter E, Lalova-Spinks T, Borry P, Valcke P, Kindt E, Negrouk A, Verhenneman G, Derèze JJ, Storme R, Huys I
Publié dans: Frontiers in Medicine, 2022, ISSN 2296-858X
Éditeur: 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

Auteurs: 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
Publié dans: IScience, Numéro 25/4, 2022, Page(s) 104101, ISSN 2589-0042
Éditeur: Cell Press, Elsevier
DOI: 10.1016/j.isci.2022.104101

Design, immunogenicity, and efficacy of a pan-sarbecovirus dendritic-cell targeting vaccine

Auteurs: 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
Publié dans: EBioMedicine, Numéro 80, 2022, Page(s) 104062, ISSN 2352-3964
Éditeur: Elsevier BV
DOI: 10.1016/j.ebiom.2022.104062

Combination of the parent analogue of remdesivir (GS-441524) and molnupiravir results in a markedly potent antiviral effect in SARS-CoV-2 infected Syrian hamsters

Auteurs: Abdelnabi R, Maes P, de Jonghe S, Weynand B, Neyts J.
Publié dans: Frontiers in Pharmacology, 2022, ISSN 1663-9812
Éditeur: Frontiers Media S.A.
DOI: 10.3389/fphar.2022.1072202

Identification of novel antiviral drug candidates using an optimized SARS-CoV-2 phenotypic screening platform

Auteurs: Bojkiva D, Reus P, Panosch L, Bechtel M, Rothenburger T, Kandler JD, Pfeiffer A, Wagner JUG, Shumliakivska M, Dimmeler S, Olmer R, Martin U, Vondran FWR, Toptan T, Rothweiler F, Zehner R, Rabenau HF, Osman KL, Pullan ST, Carroll MW, Cinatl Jr J.
Publié dans: iScience, 2023, ISSN 2589-0042
Éditeur: Cell Press Elsevier
DOI: 10.1016/j.isci.2023.105944

CD177, a specific marker of neutrophil activation, is associated with coronavirus disease 2019 severity and death

Auteurs: 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
Publié dans: iScience, Numéro 24/7, 2021, Page(s) 102711, ISSN 2589-0042
Éditeur: Cell Press Elsevier Inc.
DOI: 10.1016/j.isci.2021.102711

Neutrophil Activation and Immune Thrombosis Profiles Persist in Convalescent COVID-19

Auteurs: Hakim Hocini, Aurélie Wiedemann, Fabiola Blengio, Cécile Lefebvre, Minerva Cervantes-Gonzalez, Emile Foucat, Pascaline Tisserand, Mathieu Surenaud, Séverin Coléon, Mélanie Prague, Lydia Guillaumat, Corinne Krief, Craig Fenwick, Cédric Laouénan, Lila Bouadma, Jade Ghosn, Giuseppe Pantaleo, Rodolphe Thiébaut; French COVID cohort study group; Yves Lévy
Publié dans: J Clin Immunol, 2023, ISSN 0271-9142
Éditeur: Kluwer Academic/Plenum Publishers
DOI: 10.1007/s10875-023-01459-x

Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern

Auteurs: Vangeel L, Chiu W, De Jonghe S, Maes P, Slechten B, Raymenants J, Andre E, Leyssen P, Neyts J and Jochmans D.
Publié dans: Antiviral Research, Numéro 198, 2022, Page(s) 105252, ISSN 0166-3542
Éditeur: 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

Auteurs: 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
Publié dans: Antiviral Research, 2022, ISSN 0166-3542
Éditeur: Elsevier BV
DOI: 10.1016/j.antiviral.2022.105429

Refolding of lid subdomain of SARS-CoV-2 nsp14 upon nsp10 interaction releases exonuclease activity

Auteurs: 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.
Publié dans: Structure, Numéro 09692126, 2022, Page(s) 1050-1054, ISSN 0969-2126
Éditeur: 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

Auteurs: 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
Publié dans: Circulation, Numéro 143/8, 2021, Page(s) 865-868, ISSN 0009-7322
Éditeur: Lippincott Williams & Wilkins Ltd.
DOI: 10.1161/circulationaha.120.052824

The application of data altruism in clinical research through empirical and legal analysis lenses

Auteurs: Teodora Lalova-Spinks, Janos Meszaros, Isabelle Huys
Publié dans: Frontiers in Medicine, 2023, ISSN 2296-858X
Éditeur: Lausanne Frontiers Media
DOI: 10.3389/fmed.2023.1141685

Synthesis, Structure–Activity Relationships, and Antiviral Profiling of 1-Heteroaryl-2-Alkoxyphenyl Analogs As Inhibitors of SARS-CoV-2 Replication.

Auteurs: 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
Publié dans: Molecules, Numéro 27/3, 2022, Page(s) 1052, ISSN 1420-3049
Éditeur: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/molecules27031052

Shape-Restrained Modeling of Protein–Small-Molecule Complexes with High Ambiguity Driven DOCKing

Auteurs: Panagiotis I. Koukos, Manon Réau, Alexandre M. J. J. Bonvin
Publié dans: Journal of Chemical Information and Modeling, Numéro 61/9, 2021, Page(s) 4807-4818, ISSN 1549-9596
Éditeur: American Chemical Society
DOI: 10.1021/acs.jcim.1c00796

Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates

Auteurs: 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
Publié dans: Nature, Numéro 585/7826, 2020, Page(s) 584-587, ISSN 0028-0836
Éditeur: Nature Publishing Group
DOI: 10.1038/s41586-020-2558-4

High Throughput cryo-EM epitope mapping of SARS-CoV-2 spike protein antibodies using EPU multigrid

Auteurs: 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
Publié dans: 2022
Éditeur: ThermoFischer

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