دورية أكاديمية
Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity.
| العنوان: | Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity. |
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| المؤلفون: | Thomson EC; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK; Department of Clinical Research, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK., Rosen LE; Vir Biotechnology, San Francisco, CA 94158, USA., Shepherd JG; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Spreafico R; Vir Biotechnology, San Francisco, CA 94158, USA., da Silva Filipe A; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Wojcechowskyj JA; Vir Biotechnology, San Francisco, CA 94158, USA., Davis C; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Piccoli L; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland., Pascall DJ; Institute of Biodiversity, Animal Health and Comparative Medicine, Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow G61 1QH, UK., Dillen J; Vir Biotechnology, San Francisco, CA 94158, USA., Lytras S; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Czudnochowski N; Vir Biotechnology, San Francisco, CA 94158, USA., Shah R; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Meury M; Vir Biotechnology, San Francisco, CA 94158, USA., Jesudason N; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., De Marco A; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland., Li K; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Bassi J; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland., O'Toole A; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3FL, UK., Pinto D; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland., Colquhoun RM; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3FL, UK., Culap K; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland., Jackson B; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3FL, UK., Zatta F; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland., Rambaut A; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3FL, UK., Jaconi S; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland., Sreenu VB; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Nix J; Molecular Biology Consortium, Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA., Zhang I; Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Tri-Institutional PhD Program in Computational Biology and Medicine, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA., Jarrett RF; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Glass WG; Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Beltramello M; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland., Nomikou K; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Pizzuto M; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland., Tong L; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Cameroni E; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland., Croll TI; Cambridge Institute for Medical Research, Department of Haematology, University of Cambridge, Cambridge CB2 0XY, UK., Johnson N; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Di Iulio J; Vir Biotechnology, San Francisco, CA 94158, USA., Wickenhagen A; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Ceschi A; Faculty of Biomedical Sciences, Università della Svizzera italiana, 6900 Lugano, Switzerland; Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland; Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, 8091 Zurich, Switzerland., Harbison AM; Department of Chemistry and Hamilton Institute, Maynooth University, Maynooth, Ireland., Mair D; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Ferrari P; Department of Nephrology, Ospedale Civico Lugano, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland; Prince of Wales Hospital Clinical School, University of New South Wales, Sydney, NSW 2052, Australia., Smollett K; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Sallusto F; Institute for Research in Biomedicine, Università della Svizzera italiana, 6500 Bellinzona, Switzerland; ETH Institute of Microbiology, ETH Zurich, 8093 Zürich, Switzerland., Carmichael S; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Garzoni C; Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese Moncucco, 6900 Lugano, Switzerland., Nichols J; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Galli M; III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, 20157 Milan, Italy., Hughes J; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Riva A; III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, 20157 Milan, Italy., Ho A; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Schiuma M; III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, 20157 Milan, Italy., Semple MG; NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7BE, UK; Respiratory Medicine, Alder Hey Children's Hospital, Liverpool L12 2AP, UK., Openshaw PJM; National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK., Fadda E; Department of Chemistry and Hamilton Institute, Maynooth University, Maynooth, Ireland., Baillie JK; The Roslin Institute, University of Edinburgh, Edinburgh EH25 9RG, UK; Intensive Care Unit, Royal Infirmary Edinburgh, Edinburgh EH16 4SA, UK., Chodera JD; Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Rihn SJ; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK., Lycett SJ; The Roslin Institute, University of Edinburgh, Edinburgh EH25 9RG, UK., Virgin HW; Vir Biotechnology, San Francisco, CA 94158, USA; Washington University School of Medicine, Saint Louis, MO 63110, USA., Telenti A; Vir Biotechnology, San Francisco, CA 94158, USA., Corti D; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland., Robertson DL; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK. Electronic address: david.l.robertson@glasgow.ac.uk., Snell G; Vir Biotechnology, San Francisco, CA 94158, USA. Electronic address: gsnell@vir.bio. |
| مؤلفون مشاركون: | ISARIC4C Investigators; ISARIC4C Investigators., COVID-19 Genomics UK (COG-UK) Consortium; https://www.cogconsortium.uk. |
| المصدر: | Cell [Cell] 2021 Mar 04; Vol. 184 (5), pp. 1171-1187.e20. Date of Electronic Publication: 2021 Jan 28. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge, Ma : Cell Press Original Publication: Cambridge, MIT Press. |
| مواضيع طبية MeSH: | Genetic Fitness* , Immune Evasion*, COVID-19/*immunology , SARS-CoV-2/*genetics , Spike Glycoprotein, Coronavirus/*genetics, Angiotensin-Converting Enzyme 2/chemistry ; Antibodies, Neutralizing/genetics ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; COVID-19/virology ; Humans ; Mutation ; Phylogeny ; SARS-CoV-2/chemistry ; SARS-CoV-2/pathogenicity ; Spike Glycoprotein, Coronavirus/chemistry ; Virulence |
| مستخلص: | SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics. Competing Interests: Declaration of interests L.E.R., R. Spreafico, J.A.W., L.P., J.D., N.C., M.M., A.D.M., J.B., D.P., K.C., F.Z., S.J., M.B., M.P., E.C., J.D.I., H.W.V., A.T., D.C., and G.S. are or were employees of Vir Biotechnology and may hold shares in Vir Biotechnology. C.G. is an external scientific advisor for Humabs BioMed SA. J. Nix and T.I.C. are consultants with Vir Biotechnology. M.G.S. declares interest in Integrum Scientific, Greensboro, NC, outside the scope of this work. J.D.C. is a current member of the Scientific Advisory Board of OpenEye Scientific Software and is a scientific consultant to Foresite Labs. The Chodera laboratory (I.Z., W.G.G., and J.D.C.) receives or has received funding from multiple sources, including the NIH, the National Science Foundation, the Parker Institute for Cancer Immunotherapy, Relay Therapeutics, Entasis Therapeutics, Silicon Therapeutics, EMD Serono (Merck KGaA), AstraZeneca, Vir Biotechnology, XtalPi, the Molecular Sciences Software Institute, the Starr Cancer Consortium, the Open Force Field Consortium, Cycle for Survival, a Louis V. Gerstner Young Investigator Award, and the Sloan Kettering Institute. A complete funding history for the Chodera lab can be found at https://www.choderalab.org/funding. The other authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: Nat Rev Immunol. 2021 Mar;21(3):136. (PMID: 33542500) Comment in: Nat Rev Immunol. 2021 Mar;21(3):136. (PMID: 33542501) |
| References: | Mol Cell. 2020 Sep 3;79(5):710-727. (PMID: 32853546) Cell. 2020 May 28;181(5):1004-1015.e15. (PMID: 32375025) Nat Chem. 2021 Jul;13(7):651-659. (PMID: 34031561) Science. 2020 Aug 21;369(6506):1010-1014. (PMID: 32540901) Nature. 2020 Aug;584(7821):437-442. (PMID: 32555388) Science. 2020 Mar 13;367(6483):1260-1263. (PMID: 32075877) Sci Rep. 2018 Jul 11;8(1):10432. (PMID: 29992986) Lancet Microbe. 2020 Jul;1(3):e99-e100. (PMID: 32835336) Elife. 2020 Oct 28;9:. (PMID: 33112236) Bioinformatics. 2009 Jul 15;25(14):1754-60. (PMID: 19451168) Science. 2021 Feb 19;371(6531):850-854. (PMID: 33495308) EBioMedicine. 2020 Dec;62:103112. (PMID: 33186810) J Virol. 2004 Sep;78(17):9007-15. (PMID: 15308697) J Chem Theory Comput. 2015 Apr 14;11(4):1645-57. (PMID: 26574374) Nat Commun. 2020 Nov 26;11(1):6013. (PMID: 33243994) Science. 2000 Dec 8;290(5498):1903-4. (PMID: 17742054) J Comput Chem. 2011 Jul 30;32(10):2319-27. (PMID: 21500218) Science. 2021 Jan 8;371(6525):172-177. (PMID: 33172935) Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):355-67. (PMID: 21460454) Cell. 2021 Jan 7;184(1):64-75.e11. (PMID: 33275900) Lancet. 2020 Aug 15;396(10249):467-478. (PMID: 32702298) Nature. 2020 Jul;583(7815):290-295. (PMID: 32422645) N Engl J Med. 2020 Nov 12;383(20):1920-1931. (PMID: 32663912) N Engl J Med. 2021 Jan 21;384(3):229-237. (PMID: 33113295) Cell. 2020 Apr 16;181(2):281-292.e6. (PMID: 32155444) J Chem Theory Comput. 2015 Aug 11;11(8):3696-713. (PMID: 26574453) Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14764-9. (PMID: 9405687) Sci Transl Med. 2021 May 26;13(595):. (PMID: 33941621) Glycobiology. 2019 Jan 1;29(1):94-103. (PMID: 30325416) Cell. 2020 Aug 20;182(4):812-827.e19. (PMID: 32697968) Science. 2021 Feb 19;371(6531):823-829. (PMID: 33495307) Bioinformatics. 2019 Feb 1;35(3):526-528. (PMID: 30016406) Cell Host Microbe. 2021 Mar 10;29(3):463-476.e6. (PMID: 33592168) Science. 2020 Aug 7;369(6504):731-736. (PMID: 32540900) Trends Immunol. 2020 May;41(5):355-359. (PMID: 32249063) J Med Virol. 2020 May;92(5):501-511. (PMID: 32027035) Sci Adv. 2020 Jul 1;6(27):. (PMID: 32937441) Science. 2020 Aug 21;369(6506):1014-1018. (PMID: 32540904) Nature. 2020 May;581(7807):221-224. (PMID: 32225175) Nat Commun. 2018 Apr 11;9(1):1386. (PMID: 29643370) Proc Natl Acad Sci U S A. 2020 Sep 22;117(38):23652-23662. (PMID: 32868447) Clin Infect Dis. 2021 Dec 6;73(11):e4400-e4408. (PMID: 32897368) Protein Sci. 2021 Jan;30(1):70-82. (PMID: 32881101) Science. 2020 Aug 21;369(6506):956-963. (PMID: 32540903) Nat Commun. 2020 Sep 9;11(1):4507. (PMID: 32908126) J Chem Phys. 2013 May 7;138(17):174102. (PMID: 23656109) Biophys J. 2015 Oct 20;109(8):1528-32. (PMID: 26488642) Science. 2011 Aug 12;333(6044):850-6. (PMID: 21798894) Nature. 2021 Mar;591(7851):639-644. (PMID: 33461210) Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501. (PMID: 20383002) Science. 2020 Nov 20;370(6519):950-957. (PMID: 32972994) PLoS Comput Biol. 2017 Jul 26;13(7):e1005659. (PMID: 28746339) Cell. 2020 Sep 3;182(5):1295-1310.e20. (PMID: 32841599) Nat Microbiol. 2021 Jan;6(1):112-122. (PMID: 33349681) Cell Host Microbe. 2021 Jan 13;29(1):44-57.e9. (PMID: 33259788) N Engl J Med. 2020 Dec 10;383(24):2320-2332. (PMID: 32877576) Mol Biol Evol. 2020 May 1;37(5):1530-1534. (PMID: 32011700) Nat Microbiol. 2020 Nov;5(11):1408-1417. (PMID: 32724171) Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32. (PMID: 20124692) Science. 2005 Sep 16;309(5742):1864-8. (PMID: 16166518) Cell Host Microbe. 2021 Jan 13;29(1):23-31.e4. (PMID: 33306985) Acta Crystallogr D Struct Biol. 2018 Jun 1;74(Pt 6):519-530. (PMID: 29872003) Cell. 2020 Sep 3;182(5):1284-1294.e9. (PMID: 32730807) PLoS Biol. 2020 Dec 21;18(12):e3001016. (PMID: 33347434) Glycobiology. 2021 May 3;31(4):410-424. (PMID: 33135055) Science. 2020 Jul 17;369(6501):330-333. (PMID: 32366695) Lancet Infect Dis. 2020 Nov;20(11):1263-1272. (PMID: 32679081) ACS Cent Sci. 2020 Oct 28;6(10):1722-1734. (PMID: 33140034) Cell Host Microbe. 2020 Oct 7;28(4):586-601.e6. (PMID: 32841605) F1000Res. 2018 Dec 20;7:1961. (PMID: 30705752) Cell. 2020 Oct 29;183(3):739-751.e8. (PMID: 32991842) Genome Biol. 2019 Jan 8;20(1):8. (PMID: 30621750) J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674. (PMID: 19461840) Cell. 2020 Nov 12;183(4):1024-1042.e21. (PMID: 32991844) Bioinformatics. 2018 Sep 15;34(18):3094-3100. (PMID: 29750242) N Engl J Med. 2020 Dec 3;383(23):2291-2293. (PMID: 33176080) Nature. 2020 May;581(7807):215-220. (PMID: 32225176) Science. 2020 Dec 18;370(6523):1464-1468. (PMID: 33184236) J Virol. 2015 Nov 18;90(3):1414-23. (PMID: 26581979) J Comput Chem. 2008 Mar;29(4):622-55. (PMID: 17849372) Science. 2021 Mar 12;371(6534):1139-1142. (PMID: 33536258) Nat Microbiol. 2020 Nov;5(11):1403-1407. (PMID: 32669681) Nature. 2020 Mar;579(7798):265-269. (PMID: 32015508) |
| معلومات مُعتمدة: | COV/EDI/20/11 United Kingdom CSO_ Chief Scientist Office; MC_PC_19059 United Kingdom MRC_ Medical Research Council; MC_UU_12014/9 United Kingdom MRC_ Medical Research Council; P30 CA008748 United States CA NCI NIH HHS; MC_PC_19027 United Kingdom MRC_ Medical Research Council; R01 GM132386 United States GM NIGMS NIH HHS; MC_PC_19025 United Kingdom MRC_ Medical Research Council; United Kingdom WT_ Wellcome Trust; MC_UU_12014/10 United Kingdom MRC_ Medical Research Council; MC_UU_12014/12 United Kingdom MRC_ Medical Research Council; P30 GM124169 United States GM NIGMS NIH HHS; MR/S032304/1 United Kingdom MRC_ Medical Research Council; 201366/Z/16/Z United Kingdom WT_ Wellcome Trust; R01 GM121505 United States GM NIGMS NIH HHS; MC_UU_12014/3 United Kingdom MRC_ Medical Research Council |
| فهرسة مساهمة: | Keywords: COVID-19; N439K; SARS-CoV-2; Spike; monoclonal antibody escape; mutation; protein structure; receptor binding motif; variant |
| المشرفين على المادة: | 0 (Antibodies, Neutralizing) 0 (Antibodies, Viral) 0 (Spike Glycoprotein, Coronavirus) 0 (spike protein, SARS-CoV-2) EC 3.4.17.23 (ACE2 protein, human) EC 3.4.17.23 (Angiotensin-Converting Enzyme 2) |
| تواريخ الأحداث: | Date Created: 20210223 Date Completed: 20210311 Latest Revision: 20240211 |
| رمز التحديث: | 20240211 |
| مُعرف محوري في PubMed: | PMC7843029 |
| DOI: | 10.1016/j.cell.2021.01.037 |
| PMID: | 33621484 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1097-4172 |
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| DOI: | 10.1016/j.cell.2021.01.037 |