ArticleScience (New York, N.Y.)2023
Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors.
Open access · hybridAbstract read
In one paragraph
Article in Science (New York, N.Y.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed
32.3field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
103 citing papers in PubMed, 163 citations in OpenAlex.
- Syndirella: synthesis-directed fragment elaboration enables extensive and cost-effective binding site exploration beyond catalog compounds.Chemical science · 2026Article
- Physical priors improve performance of structure-based binding affinity models.bioRxiv : the preprint server for biology · 2026Article
- Development of Covalent Inhibitors of Chikungunya Virus nsP2 Cysteine Protease Enabled by Direct-to-Biology Synthesis and Screening.Journal of medicinal chemistry · 2026Article
- Integrated Computational Study Prioritizes Drug-like Para-Flavonoids as Candidate SARS-CoV-2 MCurrent issues in molecular biology · 2026Article
- Investigating the Binding Mode of a Naphthol-Based Inhibitor Targeting SARS-CoV-2 Main Protease.ChemMedChem · 2026Article
- Recent Advances in the Design of Inhibitors Targeting the Viral Entry and Replication of the SARS-CoV-2 Virus, Driven by In Silico Approaches.Molecules (Basel, Switzerland) · 2026Review
- Structure-based macrocyclization of α-ketoamides leads to potent inhibitors of coronaviral and enteroviral proteases.Communications chemistry · 2026Article
- Kinase inhibitors can change protonation or tautomeric state upon binding.bioRxiv : the preprint server for biology · 2026Article
- Modeling the Sensitivity of Large-Scale Virtual Screening to Scoring Function Accuracy, Artifacts, and Library Composition.Journal of chemical information and modeling · 2026Article
- Two faces of drug repurposing data in machine learning-driven structure-based virtual screening supported by interaction fingerprints.Journal of computer-aided molecular design · 2026Article
- Linking biochemical and cellular efficacy of MERS coronavirus main protease inhibitors.ACS pharmacology & translational science · 2026Article
- Article
- Absolute Binding Free Energy Calculations between the SARS-CoV-2 Main Protease and 130 Drug Leads Using Implicit Ligand Theory.Journal of chemical information and modeling · 2026Article
- Targeting SARS-CoV-2 Non-Structural Proteins: A Blueprint for Next-Generation Small-Molecule Coronavirus Antivirals.Pharmaceutics · 2026Review
- An Automated Workflow for Diagnosing Sampling Issues Caused by Slow Torsional Motions in Molecular Simulations.Journal of chemical information and modeling · 2026Article
- Linking biochemical and cellular efficacy of MERS coronavirus main protease inhibitors.bioRxiv : the preprint server for biology · 2026Article
- Evaluating generalization in protein-ligand cofolding methods.Nature structural & molecular biology · 2026Article
- Nicotine-Inspired, De Novo-Designed SARS-CoV-2 Main Protease Inhibitors Reveal Unique Chemistry for Covalently Conjugating Both Cysteine and Histidine Residues in the Catalytic Dyad.Journal of the American Chemical Society · 2026Article
- Nanoscale Direct-to-Biology Optimization of Cdk2 Inhibitors.Journal of medicinal chemistry · 2026Article
- Structure- and Ligand-Based Discovery of Novel 3-Chymotrypsin-Like Protease Nonpeptidomimetic Hits.ChemMedChem · 2026Article
43 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
213 authors at 20 institutions in 23 countries.
Melissa L Boby *Pharmacology Graduate Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
Daren Fearon *Diamond Light Source Ltd., Harwell Science and Innovation Campus, Didcot, UK.ORCID 0000-0003-3529-7863
Matteo Ferla *Oxford Biomedical Research Centre, National Institute for Health Research, University of Oxford, Oxford, UK.
Mihajlo Filep *Department of Chemical and Structural Biology, The Weizmann Institute of Science, Rehovot, Israel.ORCID 0009-0003-7288-9769
Lizbé Koekemoer *Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID 0000-0001-9226-9127
Matthew C Robinson *PostEra Inc., Cambridge, MA 02142, USA.ORCID 0009-0001-3935-9083
COVID Moonshot Consortium‡
John D ChoderaProgram in Computational and Systems Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.ORCID 0000-0003-0542-119X
Alpha A LeePostEra Inc., Cambridge, MA 02142, USA.
Nir LondonDepartment of Chemical and Structural Biology, The Weizmann Institute of Science, Rehovot, Israel.ORCID 0000-0003-2687-0699
Annette von DelftOxford Biomedical Research Centre, National Institute for Health Research, University of Oxford, Oxford, UK.ORCID 0000-0002-7699-8140
Frank von DelftDiamond Light Source Ltd., Harwell Science and Innovation Campus, Didcot, UK.ORCID 0000-0003-0378-0017
Hagit AchdoutIsrael Institute for Biological Research, Department of Infectious Diseases, Ness-Ziona, Israel.
Anthony AimonDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Dominic S AlonziUniversity of Oxford, Department of Biochemistry, Oxford Glycobiology Institute, South Parks Road, Oxford OX1 3QU, UK.
Robert ArbonSloan Kettering Institute, Memorial Sloan Kettering Cancer Center, Computational and Systems Biology Program, New York, NY 10065, USA.
Jasmin C AschenbrennerDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Blake H BalcombDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Elad Bar-DavidIsrael Institute for Biological Research, Department of Infectious Diseases, Ness-Ziona, Israel.
Haim BarrThe Weizmann Institute of Science, Wohl Institute for Drug Discovery of the Nancy and Stephen Grand Israel National Center for Personalized Medicine, Rehovot, 7610001, Israel.
Amir Ben-ShmuelIsrael Institute for Biological Research, Department of Infectious Diseases, Ness-Ziona, Israel.
James BennettUniversity of Oxford, Nuffield Department of Medicine, Centre for Medicines Discovery, Oxford, OX3 7DQ, UK.
Vitaliy A BilenkoEnamine Ltd, Kyiv, 02094, Ukraine.
Bruce BordenFolding@Home Consortium.
Pascale BouletDrugs for Neglected Diseases Initiative (DNDi), Geneva, 1202, Switzerland.
Gregory R BowmanUniversity of Pennsylvania, Departments of Biochemistry and Biophysics and Bioengineering, Philadelphia, PA 19083, USA.
Lennart BrewitzUniversity of Oxford, Department of Chemistry, Chemistry Research Laboratory, Oxford, OX1 3TA, UK.
Juliane BrunUniversity of Oxford, Department of Biochemistry, Oxford Glycobiology Institute, South Parks Road, Oxford OX1 3QU, UK.
Sarma BvnbsSai Life Sciences Limited, ICICI Knowledge Park, Shameerpet, Hyderabad 500 078, Telangana, India.
Mark CalmianoUCB, Slough, SL1 3WE, UK.
Anna CarberyDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Daniel W CarneyTakeda Development Center Americas, Inc., San Diego, CA 92121, USA.
Emma CattermoleUniversity of Oxford, Department of Biochemistry, Oxford Glycobiology Institute, South Parks Road, Oxford OX1 3QU, UK.
Edcon ChangTakeda Development Center Americas, Inc., San Diego, CA 92121, USA.
Eugene ChernyshenkoEnamine Ltd, Kyiv, 02094, Ukraine.
Austin ClydeArgonne National Lab, Lemont, IL 60439, USA.
Joseph E CofflandCauldron Development Oy, Helsinki, 00140, Finland.
Galit CohenThe Weizmann Institute of Science, Wohl Institute for Drug Discovery of the Nancy and Stephen Grand Israel National Center for Personalized Medicine, Rehovot, 7610001, Israel.
Jason C ColeCambridge Crystallographic Data Centre, Cambridge, CB2 1EZ, UK.
Alessandro ContiniUniversity of Milan, Department of General and Organic Chemistry, Milan, 20133, Italy.
Lisa CoxLife Compass Consulting Ltd, Macclesfield, SK10 5UE, UK.
Tristan Ian CrollThe University of Cambridge, Cambridge Institute for Medical Research, Department of Haematology, Cambridge CB2 0XY, UK.
Milan CvitkovicPostEra Inc., Cambridge, MA, 02142, USA.
Steven De JongheKU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
Alex DiasDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Kim DonckersKU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
David L DotsonDatryllic LLC, Phoenix AZ, 85003, USA.
Alice DouangamathDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Shirly DubersteinThe Weizmann Institute of Science, Wohl Institute for Drug Discovery of the Nancy and Stephen Grand Israel National Center for Personalized Medicine, Rehovot, 7610001, Israel.
Tim DudgeonInformatics Matters Ltd, Bicester, OX26 6JU, UK.
Louise E DunnettDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Peter EastmanStanford University, Department of Chemistry, Stanford, CA 94305, USA.
Noam ErezIsrael Institute for Biological Research, Department of Infectious Diseases, Ness-Ziona, Israel.
Charles J EyermannNortheastern University, Department of Chemistry and Chemical Biology, Boston MA 02115, USA.
Michael FairheadUniversity of Oxford, Nuffield Department of Medicine, Centre for Medicines Discovery, Oxford, OX3 7DQ, UK.
Gwen FateThames Pharma Partners LLC, Mystic, CT 06355, USA.
Oleg FedorovUniversity of Oxford, Nuffield Department of Medicine, Centre for Medicines Discovery, Oxford, OX3 7DQ, UK.
Rafaela S FernandesUniversity of Sao Paulo, Sao Carlos Institute of Physics, Sao Carlos, 13563-120, Brazil.
Lori FerrinsNortheastern University, Department of Chemistry and Chemical Biology, Boston MA 02115, USA.
Richard FosterUniversity of Leeds, School of Chemistry, Leeds, LS2 9JT, UK.
Holly FosterUniversity of Leeds, School of Chemistry, Leeds, LS2 9JT, UK.
Laurent FraisseDrugs for Neglected Diseases Initiative (DNDi), Geneva, 1202, Switzerland.
Ronen GabizonThe Weizmann Institute of Science, Department of Chemical and Structural Biology, Rehovot, 7610001, Israel.
Adolfo García-SastreIcahn School of Medicine at Mount Sinai, Department of Microbiology, New York, NY 10029, USA.
Victor O GawriljukUniversity of Sao Paulo, Sao Carlos Institute of Physics, Sao Carlos, 13563-120, Brazil.
Paul GehrtzThe Weizmann Institute of Science, Department of Chemical and Structural Biology, Rehovot, 7610001, Israel.
Carina GileadiUniversity of Oxford, Nuffield Department of Medicine, Centre for Medicines Discovery, Oxford, OX3 7DQ, UK.
Charline GiroudUniversity of Oxford, Nuffield Department of Medicine, Centre for Medicines Discovery, Oxford, OX3 7DQ, UK.
William G GlassSloan Kettering Institute, Memorial Sloan Kettering Cancer Center, Computational and Systems Biology Program, New York, NY 10065, USA.
Robert C GlenUniversity of Cambridge, Department of Chemistry, Cambridge, CB2 1EW, UK.
Itai GlinertIsrael Institute for Biological Research, Department of Infectious Diseases, Ness-Ziona, Israel.
Andre S GodoyUniversity of Sao Paulo, Sao Carlos Institute of Physics, Sao Carlos, 13563-120, Brazil.
Marian GorichkoTaras Shevchenko National University of Kyiv, Kyiv, 01601, Ukraine.
Tyler Gorrie-StoneDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Ed J GriffenMedChemica Ltd, Macclesfield, Cheshire. SK11 6PU UK.
Amna HaneefIllinois Institute of Technology, Department of Biology, Chicago IL 60616 USA.
Storm Hassell HartUniversity of Sussex, Department of Chemistry, School of Life Sciences, Brighton, East Sussex, BN1 9QJ, UK.
Jag HeerSyngene International Limited, Headington, Oxford, OX3 7BZ, UK.
Michael HenrySloan Kettering Institute, Memorial Sloan Kettering Cancer Center, Computational and Systems Biology Program, New York, NY 10065, USA.
Michelle HillUniversity of Oxford, Department of Biochemistry, Oxford Glycobiology Institute, South Parks Road, Oxford OX1 3QU, UK.
Sam HorrellDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Qiu Yu Judy HuangUniversity of Massachusetts, Chan Medical School, Department of Biochemistry and Molecular Biotechnology, Worcester MA 01655, USA.
Victor D HuliakEnamine Ltd, Kyiv, 02094, Ukraine.
Matthew F D HurleyTemple University, Department of Chemistry, Philadelphia, PA 19122, USA.
Tomer IsraelyIsrael Institute for Biological Research, Department of Infectious Diseases, Ness-Ziona, Israel.
Andrew JajackPostEra Inc., Cambridge, MA, 02142, USA.
Jitske JansenRWTH Aachen University, Institute of Experimental Medicine and Systems Biology, Aachen, 52074, Germany.
Eric JnoffUCB, Chemin du Foriest, 1420 Braine-l'Alleud, Belgium.
Dirk JochmansKU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
Tobias JohnUniversity of Oxford, Department of Chemistry, Chemistry Research Laboratory, Oxford, OX1 3TA, UK.
Benjamin KaminowSloan Kettering Institute, Memorial Sloan Kettering Cancer Center, Computational and Systems Biology Program, New York, NY 10065, USA.
Lulu KangIllinois Institute of Technology, Department of Applied Mathematics, Chicago IL 60616 USA.
Anastassia L KantsadiUniversity of Oxford, Department of Biochemistry, Oxford Glycobiology Institute, South Parks Road, Oxford OX1 3QU, UK.
Peter W KennyBerwick-on-Sea, North Coast Road, Blanchisseuse, Saint George, Trinidad and Tobago.
J L KiappesUniversity of Oxford, Department of Biochemistry, Oxford Glycobiology Institute, South Parks Road, Oxford OX1 3QU, UK.
Serhii O KinakhEnamine Ltd, Kyiv, 02094, Ukraine.
Boris KovarM2M solutions s.r.o. Žilina, 010 01, Slovakia.
Tobias KrojerUniversity of Oxford, Nuffield Department of Medicine, Centre for Medicines Discovery, Oxford, OX3 7DQ, UK.
Van Ngoc Thuy LaIllinois Institute of Technology, Department of Biology, Chicago IL 60616 USA.
Sophie Laghnimi-HahnDrugs for Neglected Diseases Initiative (DNDi), Geneva, 1202, Switzerland.
Bruce A LefkerThames Pharma Partners LLC, Mystic, CT 06355, USA.
Haim LevyIsrael Institute for Biological Research, Department of Infectious Diseases, Ness-Ziona, Israel.
Ryan M LithgoDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Ivan G LogvinenkoEnamine Ltd, Kyiv, 02094, Ukraine.
Petra LukacikDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Hannah Bruce MacdonaldSloan Kettering Institute, Memorial Sloan Kettering Cancer Center, Computational and Systems Biology Program, New York, NY 10065, USA.
Elizabeth M MacLeanUniversity of Oxford, Nuffield Department of Medicine, Centre for Medicines Discovery, Oxford, OX3 7DQ, UK.
Laetitia L MakowerUniversity of Oxford, Department of Biochemistry, Oxford Glycobiology Institute, South Parks Road, Oxford OX1 3QU, UK.
Tika R MallaUniversity of Oxford, Nuffield Department of Medicine, Centre for Medicines Discovery, Oxford, OX3 7DQ, UK.
Peter G MarplesDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Tatiana MatviiukEnamine Ltd, Kyiv, 02094, Ukraine.
Willam McCorkindalePresent address: Charm Therapeutics, London, N1C 4AG, UK.
Briana L McGovernIcahn School of Medicine at Mount Sinai, Department of Microbiology, New York, NY 10029, USA.
Sharon MelamedIsrael Institute for Biological Research, Department of Infectious Diseases, Ness-Ziona, Israel.
Kostiantyn P MelnykovEnamine Ltd, Kyiv, 02094, Ukraine.
Oleg MichurinEnamine Ltd, Kyiv, 02094, Ukraine.
Pascal MiesenRadboud University Medical Center, Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Nijmegen, 6525 GA, Netherlands.
Halina MikolajekDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Bruce F MilneUniversity of Aberdeen, Department of Chemistry, Old Aberdeen, AB24 3UE Scotland, UK.
David MinhIllinois Institute of Technology, Department of Chemistry, Chicago IL 60616 USA.
Aaron MorrisPostEra Inc., Cambridge, MA, 02142, USA.
Garrett M MorrisUniversity of Oxford, Department of Statistics, Oxford OX1 3LB, UK.
Melody Jane MorwitzerUniversity of Nebraska Medical Centre, Dept of Pathology and Microbiology, Omaha, NE 68198-5900, USA.
Demetri MoustakasRelay Therapeutics, Cambridge, MA 02139, USA.
Charles E MowbrayDrugs for Neglected Diseases Initiative (DNDi), Geneva, 1202, Switzerland.
Aline M NakamuraUniversity of Sao Paulo, Sao Carlos Institute of Physics, Sao Carlos, 13563-120, Brazil.
Jose Brandao NetoDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Johan NeytsKU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
Luong NguyenPostEra Inc., Cambridge, MA, 02142, USA.
Gabriela D NoskeUniversity of Sao Paulo, Sao Carlos Institute of Physics, Sao Carlos, 13563-120, Brazil.
Vladas OleinikovasUCB, Slough, SL1 3WE, UK.
Glaucius OlivaUniversity of Sao Paulo, Sao Carlos Institute of Physics, Sao Carlos, 13563-120, Brazil.
Gijs J OverheulRadboud University Medical Center, Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Nijmegen, 6525 GA, Netherlands.
C David OwenDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Ruby PaiPostEra Inc., Cambridge, MA, 02142, USA.
Jin PanPostEra Inc., Cambridge, MA, 02142, USA.
Nir ParanIsrael Institute for Biological Research, Department of Infectious Diseases, Ness-Ziona, Israel.
Alexander Matthew PayneSloan Kettering Institute, Memorial Sloan Kettering Cancer Center, Computational and Systems Biology Program, New York, NY 10065, USA.
Benjamin PerryDrugs for Neglected Diseases Initiative (DNDi), Geneva, 1202, Switzerland.
Maneesh PingleSai Life Sciences Limited, ICICI Knowledge Park, Shameerpet, Hyderabad 500 078, Telangana, India.
Jakir PinjariSai Life Sciences Limited, ICICI Knowledge Park, Shameerpet, Hyderabad 500 078, Telangana, India.
Boaz PolitiIsrael Institute for Biological Research, Department of Infectious Diseases, Ness-Ziona, Israel.
Ailsa PowellDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Vladimír PšenákM2M solutions s.r.o. Žilina, 010 01, Slovakia.
Iván PulidoSloan Kettering Institute, Memorial Sloan Kettering Cancer Center, Computational and Systems Biology Program, New York, NY 10065, USA.
Reut PuniIsrael Institute for Biological Research, Department of Infectious Diseases, Ness-Ziona, Israel.
Victor L RangelUniversity of São Paulo, Ribeirão Preto School of Pharmaceutical Sciences, Ribeirão Preto - SP/CEP 14040-903, Brazil.
Rambabu N ReddiThe Weizmann Institute of Science, Department of Chemical and Structural Biology, Rehovot, 7610001, Israel.
Paul ReesCompass Bussiness Partners Ltd, Southcliffe, Bucks, SL9 0PD, UK.
St Patrick ReidUniversity of Nebraska Medical Centre, Dept of Pathology and Microbiology, Omaha, NE 68198-5900, USA.
Lauren ReidMedChemica Ltd, Macclesfield, Cheshire. SK11 6PU UK.
Efrat ResnickThe Weizmann Institute of Science, Department of Chemical and Structural Biology, Rehovot, 7610001, Israel.
Emily Grace RipkaPostEra Inc., Cambridge, MA, 02142, USA.
Ralph P RobinsonThames Pharma Partners LLC, Mystic, CT 06355, USA.
Jaime Rodriguez-GuerraCharité - Universitätsmedizin Berlin, In silico Toxicology and Structural Bioinformatics, Berlin, 10117, Germany.
Romel RosalesIcahn School of Medicine at Mount Sinai, Department of Microbiology, New York, NY 10029, USA.
Dominic A RufaSloan Kettering Institute, Memorial Sloan Kettering Cancer Center, Computational and Systems Biology Program, New York, NY 10065, USA.
Kadi SaarUniversity of Cambridge, Cavendish Laboratory, Cambridge, CB3 0HE UK.
Kumar Singh SaikatenduTakeda Development Center Americas, Inc., San Diego, CA 92121, USA.
Eidarus SalahUniversity of Oxford, Department of Chemistry, Chemistry Research Laboratory, Oxford, OX1 3TA, UK.
David SchallerCharité - Universitätsmedizin Berlin, In silico Toxicology and Structural Bioinformatics, Berlin, 10117, Germany.
Jenke ScheenSloan Kettering Institute, Memorial Sloan Kettering Cancer Center, Computational and Systems Biology Program, New York, NY 10065, USA.
Celia A SchifferUniversity of Massachusetts, Chan Medical School, Department of Biochemistry and Molecular Biotechnology, Worcester MA 01655, USA.
Christopher J SchofieldUniversity of Oxford, Department of Chemistry, Chemistry Research Laboratory, Oxford, OX1 3TA, UK.
Mikhail ShafeevEnamine Ltd, Kyiv, 02094, Ukraine.
Aarif ShaikhSai Life Sciences Limited, ICICI Knowledge Park, Shameerpet, Hyderabad 500 078, Telangana, India.
Ala M ShaqraUniversity of Massachusetts, Chan Medical School, Department of Biochemistry and Molecular Biotechnology, Worcester MA 01655, USA.
Jiye ShiUCB, Chemin du Foriest, 1420 Braine-l'Alleud, Belgium.
Khriesto ShurrushThe Weizmann Institute of Science, Wohl Institute for Drug Discovery of the Nancy and Stephen Grand Israel National Center for Personalized Medicine, Rehovot, 7610001, Israel.
Sukrit SinghSloan Kettering Institute, Memorial Sloan Kettering Cancer Center, Computational and Systems Biology Program, New York, NY 10065, USA.
Assa SittnerIsrael Institute for Biological Research, Department of Infectious Diseases, Ness-Ziona, Israel.
Peter SjöDrugs for Neglected Diseases Initiative (DNDi), Geneva, 1202, Switzerland.
Rachael SkynerDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Adam SmalleyUCB, Slough, SL1 3WE, UK.
Bart SmeetsRadboud University Medical Center, Department of pathology, Radboud Institute for Molecular Life Sciences, Nijmegen, 6525 GA, Netherlands.
Mihaela D SmilovaUniversity of Oxford, Nuffield Department of Medicine, Centre for Medicines Discovery, Oxford, OX3 7DQ, UK.
Leonardo J SolmeskyThe Weizmann Institute of Science, Wohl Institute for Drug Discovery of the Nancy and Stephen Grand Israel National Center for Personalized Medicine, Rehovot, 7610001, Israel.
John SpencerUniversity of Sussex, Department of Chemistry, School of Life Sciences, Brighton, East Sussex, BN1 9QJ, UK.
Claire Strain-DamerellDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Vishwanath SwamySai Life Sciences Limited, ICICI Knowledge Park, Shameerpet, Hyderabad 500 078, Telangana, India.
Hadas TamirIsrael Institute for Biological Research, Department of Infectious Diseases, Ness-Ziona, Israel.
Jenny C TaylorUniversity of Oxford, Nuffield Department of Medicine, Wellcome Centre for Human Genetics, Oxford OX3 7BN, UK.
Rachael E TennantLhasa Limited, Leeds, LS11 5PS, UK.
Warren ThompsonDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Andrew ThompsonUniversity of Oxford, Nuffield Department of Medicine, Centre for Medicines Discovery, Oxford, OX3 7DQ, UK.
Susana TomásioCollaborative Drug Discovery, Cambridge, CB2 1GE, UK.
Charles W E TomlinsonDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Igor S TsurupaEnamine Ltd, Kyiv, 02094, Ukraine.
Anthony TumberUniversity of Oxford, Department of Chemistry, Chemistry Research Laboratory, Oxford, OX1 3TA, UK.
Ioannis VakonakisUniversity of Oxford, Department of Biochemistry, Oxford Glycobiology Institute, South Parks Road, Oxford OX1 3QU, UK.
Ronald P van RijRadboud University Medical Center, Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Nijmegen, 6525 GA, Netherlands.
Laura VangeelKU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
Finny S VargheseRadboud University Medical Center, Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Nijmegen, 6525 GA, Netherlands.
Mariana VaschettoCollaborative Drug Discovery, Cambridge, CB2 1GE, UK.
Einat B VitnerIsrael Institute for Biological Research, Department of Infectious Diseases, Ness-Ziona, Israel.
Vincent VoelzTemple University, Department of Chemistry, Philadelphia, PA 19122, USA.
Andrea VolkamerCharité - Universitätsmedizin Berlin, In silico Toxicology and Structural Bioinformatics, Berlin, 10117, Germany.
Martin A WalshDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Walter WardWalter Ward Consultancy and Training, Derbyshire, SK22 4AA, UK.
Charlie WeatherallCollaborative Drug Discovery, Burlingame, CA 94010, USA.
Shay WeissIsrael Institute for Biological Research, Department of Infectious Diseases, Ness-Ziona, Israel.
Kris M WhiteIcahn School of Medicine at Mount Sinai, Department of Microbiology, New York, NY 10029, USA.
Conor Francis WildDiamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
Karolina D WittUniversity of Oxford, Nuffield Department of Medicine, Pandemic Sciences Institute, Oxford, Oxon, OX3 7DQ, UK.
Matthew WittmannSloan Kettering Institute, Memorial Sloan Kettering Cancer Center, Computational and Systems Biology Program, New York, NY 10065, USA.
Nathan WrightUniversity of Oxford, Nuffield Department of Medicine, Centre for Medicines Discovery, Oxford, OX3 7DQ, UK.
Yfat Yahalom-RonenIsrael Institute for Biological Research, Department of Infectious Diseases, Ness-Ziona, Israel.
Nese Kurt YilmazUniversity of Massachusetts, Chan Medical School, Department of Biochemistry and Molecular Biotechnology, Worcester MA 01655, USA.
Daniel ZaidmannThe Weizmann Institute of Science, Department of Chemical and Structural Biology, Rehovot, 7610001, Israel.
Ivy ZhangSloan Kettering Institute, Memorial Sloan Kettering Cancer Center, Computational and Systems Biology Program, New York, NY 10065, USA.
Hadeer ZidaneThe Weizmann Institute of Science, Wohl Institute for Drug Discovery of the Nancy and Stephen Grand Israel National Center for Personalized Medicine, Rehovot, 7610001, Israel.
Nicole ZitzmannUniversity of Oxford, Department of Biochemistry, Oxford Glycobiology Institute, South Parks Road, Oxford OX1 3QU, UK.
Sarah N ZvornicaninUniversity of Massachusetts, Chan Medical School, Department of Biochemistry and Molecular Biotechnology, Worcester MA 01655, USA.
Diamond Light Source · GBIsrael Institute for Biological Research · ILMemorial Sloan Kettering Cancer Center · USUniversity of Oxford · GBWeizmann Institute of Science · ILNuffield Orthopaedic Centre · GBIdera Pharmaceuticals (United States) · USEnamine (Ukraine) · UADrugs for Neglected Diseases Initiative · CHLaurus labs (India) · INRadboud University Nijmegen · NLRega Institute for Medical Research · BEUniversity of Massachusetts Chan Medical School · USIllinois Institute of Technology · USInstitute of Physics · PLUniversity of Cambridge · GBCharité - Universitätsmedizin Berlin · DEIcahn School of Medicine at Mount Sinai · USPartners In Care · USTakeda (United States) · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MOpen data-driven infrastructure for building biomolecular force fields for predictive biophysics and drug designR01GM132386 · NIGMS · UNIVERSITY OF COLORADO · PI SHIRTS, MICHAEL R · 2020 to 2023
$3.1MMarkov State Model approaches for folding, binding and designR01GM123296 · NIGMS · TEMPLE UNIV OF THE COMMONWEALTH · PI VOELZ, VINCENT · 2017 to 2025
$3.1MMSMs, adaptive sampling, and data sharing on the cloudR01GM124007 · NIGMS · WASHINGTON UNIVERSITY · PI BOWMAN, GREGORY · 2017 to 2021
$2.0MThe role of reorganization energy in achieving selective kinase inhibition"R01GM121505 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI CHODERA, JOHN DAMON · 2017 to 2021
$1.8MStructural basis for ApoE4-induced Alzheimer's diseaseRF1AG067194 · NIA · WASHINGTON UNIVERSITY · PI BOWMAN, GREGORY · 2021 to 2021
$1.8MNCI NIH HHS P30 CA008748NIA NIH HHS RF1 AG067194NIGMS NIH HHS R01 GM121505NIGMS NIH HHS R01 GM123296NIGMS NIH HHS R01 GM124007NIGMS NIH HHS R01 GM132386Wellcome Trust 209407
Abstract
We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>490 ligand-bound x-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2400 compounds) for this campaign were shared rapidly and openly, creating a rich, open, and intellectual property-free knowledge base for future anticoronavirus drug discovery.
Indexed as
Coronavirus 3C ProteasesCoronavirus Protease InhibitorsCOVID-19 Drug TreatmentDrug DiscoverySARS-CoV-2Crystallography, X-RayHumansMolecular Docking SimulationStructure-Activity Relationship3C-like proteinase, SARS-CoV-2Coronavirus 3C ProteasesCoronavirus Protease Inhibitors
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.