Swift COronavirus therapeutics REsponse

Project Information

SCORE

Grant agreement ID: 101003627

DOI 10.3030/101003627

Project closed

EC signature date 8 April 2020

Start date 1 April 2020

End date 30 September 2022

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost € 2 627 551,25

EU contribution € 2 576 062,50

Coordinated by

ACADEMISCH ZIEKENHUIS LEIDEN
Netherlands

Deliverables

Documents, reports (6)

Crystal structure of free 2019-nCoV Mpro and complex with 13b
Characterization of nCoV standard strain

A prototype strain has been selected and its replication cycle characterized in cell lines suitable for antiviral studies.

Cross-consortium peer-reviewed publication on SCORE's overall achievements

Full overview of SCOREs achievements on the public homepage of the SCORE website wwwscorecoveu

Enzymatic assays for proteases, MTases & RdRp

At least two enzymatic assays are available in HTPS format to screen for inhibitors.

Miniaturized HTPS ExoN assay

A miniaturized HTPS ExoN assay in 96-well and 384-well format will be developed.

Gender equality report

Demonstrators, pilots, prototypes (3)

Panel of nCoV of isolates

At least 3 different nCoV isolates will be available for testing the spectrum of activity of inhibitors.

Project website and social media presence
Reverse genetics system

An nCoV full-length cDNA clone is available and this has been used to recover infectious nCoV from (RNA-) transfected mammalian cells.

Publications

Peer reviewed articles (20)

COVID-19 and the intensive care unit: vaccines to the rescue

Author(s): Kai Dallmeier, Geert Meyfroidt, Johan Neyts
Published in: Intensive Care Medicine, Issue 47/7, 2021, Page(s) 786-789, ISSN 0342-4642
Publisher: Springer Verlag
DOI: 10.1007/s00134-021-06414-1

Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis

Author(s): Ashleigh Shannon, Barbara Selisko, Nhung-Thi-Tuyet Le, Johanna Huchting, Franck Touret, Géraldine Piorkowski, Véronique Fattorini, François Ferron, Etienne Decroly, Chris Meier, Bruno Coutard, Olve Peersen, Bruno Canard
Published in: Nature Communications, Issue 11/1, 2020, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-020-18463-z

Identification of non-covalent SARS-CoV-2 main protease inhibitors by a virtual screen of commercially available drug-like compounds

Author(s): Linlin Zhang, McClane Howland, Rolf Hilgenfeld, Marc O. Anderson, Scott Eagon
Published in: Bioorganic & Medicinal Chemistry Letters, Issue 41, 2021, Page(s) 127990, ISSN 0960-894X
Publisher: Pergamon Press Ltd.
DOI: 10.1016/j.bmcl.2021.127990

A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate

Author(s): Lorena Sanchez-Felipe, Thomas Vercruysse, Sapna Sharma, Ji Ma, Viktor Lemmens, Dominique Van Looveren, Mahadesh Prasad Arkalagud Javarappa, Robbert Boudewijns, Bert Malengier-Devlies, Laurens Liesenborghs, Suzanne J. F. Kaptein, Carolien De Keyzer, Lindsey Bervoets, Sarah Debaveye, Madina Rasulova, Laura Seldeslachts, Li-Hsin Li, Sander Jansen, Michael Bright Yakass, Babs E. Verstrepen, Kinga P. B
Published in: Nature, Issue 590/7845, 2021, Page(s) 320-325, ISSN 0028-0836
Publisher: Nature Publishing Group
DOI: 10.1038/s41586-020-3035-9

Drugs against SARS‐CoV ‐2: What do we know about their mode of action?

Author(s): Coralie Valle, Baptiste Martin, Franck Touret, Ashleigh Shannon, Bruno Canard, Jean‐Claude Guillemot, Bruno Coutard, Etienne Decroly
Published in: Reviews in Medical Virology, 2020, ISSN 1052-9276
Publisher: John Wiley & Sons Inc.
DOI: 10.1002/rmv.2143

In vitro activity of itraconazole against SARS‐CoV‐2

Author(s): Ellen Van Damme, Sandra De Meyer, Denisa Bojkova, Sandra Ciesek, Jindrich Cinatl, Steven De Jonghe, Dirk Jochmans, Pieter Leyssen, Christophe Buyck, Johan Neyts, Marnix Van Loock
Published in: Journal of Medical Virology, Issue 93/7, 2021, Page(s) 4454-4460, ISSN 0146-6615
Publisher: John Wiley & Sons Inc.
DOI: 10.1002/jmv.26917

A fluorescence-based high throughput-screening assay for the SARS-CoV RNA synthesis complex

Author(s): Cecilia Eydoux, Veronique Fattorini, Ashleigh Shannon, Thi-Tuyet-Nhung Le, Bruno Didier, Bruno Canard, Jean-Claude Guillemot
Published in: Journal of Virological Methods, Issue 288, 2021, Page(s) 114013, ISSN 0166-0934
Publisher: Elsevier BV
DOI: 10.1016/j.jviromet.2020.114013

Favipiravir at high doses has potent antiviral activity in SARS-CoV-2−infected hamsters, whereas hydroxychloroquine lacks activity

Author(s): Suzanne J. F. Kaptein, Sofie Jacobs, Lana Langendries, Laura Seldeslachts, Sebastiaan ter Horst, Laurens Liesenborghs, Bart Hens, Valentijn Vergote, Elisabeth Heylen, Karine Barthelemy, Elke Maas, Carolien De Keyzer, Lindsey Bervoets, Jasper Rymenants, Tina Van Buyten, Xin Zhang, Rana Abdelnabi, Juanita Pang, Rachel Williams, Hendrik Jan Thibaut, Kai Dallmeier, Robbert Boudewijns, Jens Wouters, Pa
Published in: Proceedings of the National Academy of Sciences, Issue 117/43, 2020, Page(s) 26955-26965, ISSN 0027-8424
Publisher: National Academy of Sciences
DOI: 10.1073/pnas.2014441117

A molecular pore spans the double membrane of the coronavirus replication organelle

Author(s): Georg Wolff, Ronald W. A. L. Limpens, Jessika C. Zevenhoven-Dobbe, Ulrike Laugks, Shawn Zheng, Anja W. M. de Jong, Roman I. Koning, David A. Agard, Kay Grünewald, Abraham J. Koster, Eric J. Snijder, Montserrat Bárcena
Published in: Science, Issue 369/6509, 2020, Page(s) 1395-1398, ISSN 0036-8075
Publisher: American Association for the Advancement of Science
DOI: 10.1126/science.abd3629

The nucleotide addition cycle of the SARS-CoV-2 polymerase

Author(s): Subhas Chandra Bera, Mona Seifert, Robert N. Kirchdoerfer, Pauline van Nies, Yibulayin Wubulikasimu, Salina Quack, Flávia S. Papini, Jamie J. Arnold, Bruno Canard, Craig E. Cameron, Martin Depken, David Dulin
Published in: Cell Reports, 2021, Page(s) 109650, ISSN 2211-1247
Publisher: Cell Press
DOI: 10.1016/j.celrep.2021.109650

A prospect on the use of antiviral drugs to control local outbreaks of COVID-19

Author(s): Andrea Torneri, Pieter Libin, Joris Vanderlocht, Anne-Mieke Vandamme, Johan Neyts, Niel Hens
Published in: BMC Medicine, Issue 18/1, 2020, ISSN 1741-7015
Publisher: BioMed Central
DOI: 10.1186/s12916-020-01636-4

Inhibition of SARS-CoV-2 polymerase by nucleotide analogs from a single-molecule perspective

Author(s): Mona Seifert, Subhas C Bera, Pauline van Nies, Robert N Kirchdoerfer, Ashleigh Shannon, Thi-Tuyet-Nhung Le, Xiangzhi Meng, Hongjie Xia, James M Wood, Lawrence D Harris, Flavia S Papini, Jamie J Arnold, Steven Almo, Tyler L Grove, Pei-Yong Shi, Yan Xiang, Bruno Canard, Martin Depken, Craig E Cameron, David Dulin
Published in: eLife, Issue 10, 2021, ISSN 2050-084X
Publisher: eLife Sciences Publications
DOI: 10.7554/elife.70968

Itraconazole for COVID-19: preclinical studies and a proof-of-concept randomized clinical trial

Author(s): Laurens Liesenborghs, Isabel Spriet, Dirk Jochmans, Ann Belmans, Iwein Gyselinck, Laure-Anne Teuwen, Sebastiaan ter Horst, Erwin Dreesen, Tatjana Geukens, Matthias M. Engelen, Ewout Landeloos, Vincent Geldhof, Helga Ceunen, Barbara Debaveye, Bert Vandenberk, Lorenz Van der Linden, Sofie Jacobs, Lana Langendries, Robbert Boudewijns, Thuc Nguyen Dan Do, Winston Chiu, Xinyu Wang, Xin Zhang, Birgit We
Published in: EBioMedicine, Issue 66, 2021, Page(s) 103288, ISSN 2352-3964
Publisher: Elsevier BV
DOI: 10.1016/j.ebiom.2021.103288

SARS-CoV-2 Mpro inhibitors and activity-based probes for patient-sample imaging

Author(s): Wioletta Rut, Katarzyna Groborz, Linlin Zhang, Xinyuanyuan Sun, Mikolaj Zmudzinski, Bartlomiej Pawlik, Xinyu Wang, Dirk Jochmans, Johan Neyts, Wojciech Młynarski, Rolf Hilgenfeld, Marcin Drag
Published in: Nature Chemical Biology, Issue 17/2, 2021, Page(s) 222-228, ISSN 1552-4450
Publisher: Nature Publishing Group
DOI: 10.1038/s41589-020-00689-z

The enzymatic activity of the nsp14 exoribonuclease is critical for replication of MERS-CoV and SARS-CoV-2

Author(s): Natacha S. Ogando, Jessika C. Zevenhoven-Dobbe, Yvonne van der Meer, Peter J. Bredenbeek, Clara C. Posthuma, Eric J. Snijder
Published in: Journal of Virology, 2020, ISSN 0022-538X
Publisher: American Society for Microbiology
DOI: 10.1128/jvi.01246-20

STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters

Author(s): Robbert Boudewijns, Hendrik Jan Thibaut, Suzanne J. F. Kaptein, Rong Li, Valentijn Vergote, Laura Seldeslachts, Johan Van Weyenbergh, Carolien De Keyzer, Lindsey Bervoets, Sapna Sharma, Laurens Liesenborghs, Ji Ma, Sander Jansen, Dominique Van Looveren, Thomas Vercruysse, Xinyu Wang, Dirk Jochmans, Erik Martens, Kenny Roose, Dorien De Vlieger, Bert Schepens, Tina Van Buyten, Sofie Jacobs, Yanan Li
Published in: Nature Communications, Issue 11/1, 2020, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-020-19684-y

Comparing infectivity and virulence of emerging SARS-CoV-2 variants in Syrian hamsters

Author(s): Rana Abdelnabi, Robbert Boudewijns, Caroline S. Foo, Laura Seldeslachts, Lorena Sanchez-Felipe, Xin Zhang, Leen Delang, Piet Maes, Suzanne J.F. Kaptein, Birgit Weynand, Greetje Vande Velde, Johan Neyts, Kai Dallmeier
Published in: EBioMedicine, Issue 68, 2021, Page(s) 103403, ISSN 2352-3964
Publisher: Elsevier BV
DOI: 10.1016/j.ebiom.2021.103403

Medical treatment options for COVID-19

Author(s): Leen Delang, Johan Neyts
Published in: European Heart Journal: Acute Cardiovascular Care, Issue 9/3, 2020, Page(s) 209-214, ISSN 2048-8726
Publisher: SAGE Publications Ltd
DOI: 10.1177/2048872620922790

The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model

Author(s): Rana Abdelnabi, Caroline S. Foo, Suzanne J.F. Kaptein, Xin Zhang, Thuc Nguyen Dan Do, Lana Langendries, Laura Vangeel, Judith Breuer, Juanita Pang, Rachel Williams, Valentijn Vergote, Elisabeth Heylen, Pieter Leyssen, Kai Dallmeier, Lotte Coelmont, Arnab K. Chatterjee, Raf Mols, Patrick Augustijns, Steven De Jonghe, Dirk Jochmans, Birgit Weynand, Johan Neyts
Published in: EBioMedicine, Issue 72, 2021, Page(s) 103595, ISSN 2352-3964
Publisher: Elsevier BV
DOI: 10.1016/j.ebiom.2021.103595

Molnupiravir Inhibits Replication of the Emerging SARS-CoV-2 Variants of Concern in a Hamster Infection Model

Author(s): Rana Abdelnabi, Caroline S Foo, Steven De Jonghe, Piet Maes, Birgit Weynand, Johan Neyts
Published in: The Journal of Infectious Diseases, Issue 224/5, 2021, Page(s) 749-753, ISSN 0022-1899
Publisher: University of Chicago Press
DOI: 10.1093/infdis/jiab361

Intellectual Property Rights

Patent (1)

ANTIVIRAL SUBSTANCES WITH A WIDE SPECTRUM OF ACTIVITY

Application/Publication number: 20 21100129
Date: 2021-02-09