SARS-CoV-2 variants evolve convergent strategies to remodel the host response.

Autor:	Bouhaddou M; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology, Immunology, and Molecular Genetics (MIMG), University of California, Los Angeles, Los Angeles, CA, USA; Institute for Quantitative and Computational Biosciences (QCBio), University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA., Reuschl AK; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Division of Infection and Immunity, University College London, London, UK., Polacco BJ; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Thorne LG; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Division of Infection and Immunity, University College London, London, UK., Ummadi MR; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Ye C; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Texas Biomedical Research Institute, San Antonio, TX, USA., Rosales R; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Pelin A; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Batra J; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Jang GM; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Xu J; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Moen JM; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Richards AL; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Zhou Y; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Harjai B; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Stevenson E; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Rojc A; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Ragazzini R; Division of Infection and Immunity, University College London, London, UK; Epithelial Stem Cell Biology and Regenerative Medicine Laboratory, The Francis Crick Institute, London, UK., Whelan MVX; Division of Infection and Immunity, University College London, London, UK., Furnon W; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK., De Lorenzo G; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK., Cowton V; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK., Syed AM; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA., Ciling A; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA., Deutsch N; School of Computer Science, Tel Aviv University, Tel Aviv, Israel., Pirak D; School of Electrical Engineering, Tel Aviv University, Tel Aviv, Israel., Dowgier G; COVID Surveillance Unit, The Francis Crick Institute, London, UK., Mesner D; Division of Infection and Immunity, University College London, London, UK., Turner JL; Division of Infection and Immunity, University College London, London, UK., McGovern BL; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Rodriguez ML; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Leiva-Rebollo R; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Dunham AS; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, UK; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Saffron Walden, UK., Zhong X; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Eckhardt M; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Fossati A; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Liotta NF; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA., Kehrer T; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Cupic A; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Rutkowska M; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Mena I; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Aslam S; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Hoffert A; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Foussard H; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Olwal CO; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra, Ghana; Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Accra, Ghana., Huang W; Huffington Center for Cell-based Research in Parkinson's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Zwaka T; Huffington Center for Cell-based Research in Parkinson's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Pham J; Synthego Corporation, Redwood City, CA, USA., Lyons M; Synthego Corporation, Redwood City, CA, USA., Donohue L; Synthego Corporation, Redwood City, CA, USA., Griffin A; Synthego Corporation, Redwood City, CA, USA., Nugent R; Synthego Corporation, Redwood City, CA, USA., Holden K; Synthego Corporation, Redwood City, CA, USA., Deans R; Synthego Corporation, Redwood City, CA, USA., Aviles P; Pharma Mar S.A, Madrid, Spain., Lopez-Martin JA; Pharma Mar S.A, Madrid, Spain., Jimeno JM; Pharma Mar S.A, Madrid, Spain., Obernier K; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Fabius JM; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Soucheray M; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Hüttenhain R; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Jungreis I; MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Kellis M; MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Echeverria I; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA., Verba K; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA., Bonfanti P; Division of Infection and Immunity, University College London, London, UK; Epithelial Stem Cell Biology and Regenerative Medicine Laboratory, The Francis Crick Institute, London, UK., Beltrao P; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, UK; Institute of Molecular Systems Biology, Department of Biology, ETH Zürich, Zurich, Switzerland., Sharan R; School of Computer Science, Tel Aviv University, Tel Aviv, Israel., Doudna JA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA., Martinez-Sobrido L; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Texas Biomedical Research Institute, San Antonio, TX, USA., Patel AH; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK., Palmarini M; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK., Miorin L; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., White K; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Swaney DL; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA., Garcia-Sastre A; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: adolfo.garcia-sastre@mssm.edu., Jolly C; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Division of Infection and Immunity, University College London, London, UK. Electronic address: c.jolly@ucl.ac.uk., Zuliani-Alvarez L; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA. Electronic address: lzulianialvarez@gmail.com., Towers GJ; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Division of Infection and Immunity, University College London, London, UK. Electronic address: g.towers@ucl.ac.uk., Krogan NJ; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA; QBI Coronavirus Research Group (QCRG), University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA. Electronic address: nevan.krogan@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2023 Oct 12; Vol. 186 (21), pp. 4597-4614.e26. Date of Electronic Publication: 2023 Sep 21.
DOI:	10.1016/j.cell.2023.08.026
Abstrakt:	SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forces driving VOC evolution. We discovered that VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions. Integrative computational analyses revealed that although Alpha, Beta, Gamma, and Delta ultimately converged to suppress interferon-stimulated genes (ISGs), Omicron BA.1 did not. ISG suppression correlated with the expression of viral innate immune antagonist proteins, including Orf6, N, and Orf9b, which we mapped to specific mutations. Later Omicron subvariants BA.4 and BA.5 more potently suppressed innate immunity than early subvariant BA.1, which correlated with Orf6 levels, although muted in BA.4 by a mutation that disrupts the Orf6-nuclear pore interaction. Our findings suggest that SARS-CoV-2 convergent evolution overcame human adaptive and innate immune barriers, laying the groundwork to tackle future pandemics. Competing Interests: Declaration of interests The Krogan Laboratory received research support from Vir Biotechnology, F. Hoffmann-La Roche, and Rezo Therapeutics. N.J.K. has previously held financially compensated consulting agreements with the Icahn School of Medicine at Mount Sinai, New York and Twist Bioscience Corp. He currently has financially compensated consulting agreements with Maze Therapeutics, Interline Therapeutics, Rezo Therapeutics, and GEn1E Lifesciences, Inc. He is on the Board of Directors of Rezo Therapeutics and is a shareholder in Tenaya Therapeutics, Maze Therapeutics, Rezo Therapeutics, and Interline Therapeutics. The A.G.-S. laboratory received research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, PharmaMar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories, and Merck. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Vaxalto, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, PharmaMar, Paratus, CureLab Oncology, CureLab Veterinary, Synairgen, and Pfizer. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott, and Astrazeneca. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York. M.B. is a financially compensated scientific advisor for GEn1E Lifesciences. C.Y. and L.M.-S. are co-inventors on a patent application directed to reverse genetics approaches to generate recombinant SARS-CoV-2. The Regents of the University of California have patents issued and pending for CRISPR technologies on which J.A.D. is an inventor. J.A.D. is a co-founder of Caribou Biosciences, Editas Medicine, Scribe Therapeutics, Intellia Therapeutics, and Mammoth Biosciences. J.A.D. is a scientific advisory board member of Vertex, Caribou Biosciences, Intellia Therapeutics, Scribe Therapeutics, Mammoth Biosciences, Algen Biotechnologies, Felix Biosciences, The Column Group, and Inari. J.A.D. is Chief Science Advisor to Sixth Street, a Director at Johnson & Johnson, Altos, and Tempus, and has research projects sponsored by Apple Tree Partners and Roche. John Pham, Molly Lyons, Laura Donahue, Aliesha Griffin, Rebecca Nugent, Kevin Holden, and Robert Deans are employees and shareholders of Synthego Corporation. D.L.S. has financially compensated consulting agreements with Maze Therapeutics and Rezo Therapeutics. P.A., J.A.L.-M., and J.M.J. are employees and shareholders of Pharma Mar, S.A. (Madrid, Spain). J.A.L.-M. is a co-inventor of a patent for Plitidepsin (WO2008135793A1). J.M.J. holds stocks of Pangaea Oncology, has a non-remunerated role in the Scientific Advisory Board, and holds stocks of Promontory Therapeutics, and is a co-inventor of two patents for Plitidepsin (WO99-42125). (Copyright © 2023 Elsevier Inc. All rights reserved.)
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