SARS-CoV-2 spike protein mutations

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SARS-CoV-2 stands for Severe Acute Respiratory Syndrome - Corona Virus 2. The SARS-CoV-2 coronavirus causes COVID-19 (COrona VIrus Disease 2019). SARS-CoV-2 was numbered "2" because another coronavirus, SARS-CoV, caused an epidemic in 2002-2003. The genes of SARS-CoV-2 are in RNA. Viruses with RNA genomes tend to mutate faster than do viruses with DNA genomes[1][2]. For example, a new influenza vaccine is needed every year due to mutations, and a single drug against HIV quickly becomes ineffective due to mutations. It is no surprise that SARS-CoV-2 is mutating.

Contents

Movies for Slides

The movie at right (a multi-GIF, not interactive) can be dropped into a slide (Powerpoint, slides.google.com, libre office, etc.). It will animate when the slide is projected ("slide show" mode). This shows the priming conformational change, whereas the interactive scenes above show the static open conformation. The scenes above show all atoms, while the movie shows only alpha carbons. As above for lineage B.1.1.7: each chain of the homo-trimer is a different color; Four mutations (black); ACE2 binding site; furin cleavage site. To DOWNLOAD these files, right click, then save link as:

Please credit Proteopedia.Org in accord with our license, and Wrobel and coworkers[45] for their cryo-EM structures.

Acknowledgements

Thanks to Shoshana Wodak, Iddo Friedberg, S. Krishnaswamy and Joel Sussman for suggestions that improved this article. Eric Martz wishes to thank Jaime Prilusky and Joel Sussman for their constant efforts over more than a decade that have made Proteopedia what it is today. Thanks also to the newer members of the Proteopedia:Team.

Update History

This article was initially posted December 22, 2020. Subsequent updates:

  • December 23, 2020: Full name of SARS corrected. Citation added[20].
  • December 24, 2020: Added further evidence of the international pre-eminence of the UK coronavirus sequencing consortium[37][38]. Added Acknowledgements.
  • December 25, 2020: Added two citations[8][12] and added mention of the South African lineage without specific mutations.
  • December 27, 2020: Added this section Update History. Named and visualized the specific mutations of concern in the South African lineage 501Y.V2, with a new citation[10].
  • December 29, 2020: Added two references documenting detection of B.1.1.7 in at least 19 countries[41][42].
  • December 30, 2020: Added study showing no increased hospitalization or death for B.1.1.7 compared to wild type SARS-CoV-2[7].
  • January 4, 2021: Added evidence that the mutant lineages are more contagious[13].
  • January 5, 2021: Added a new subsection about concerns over vaccine effectiveness, with two new references[24][46].
  • January 6, 2021: Cited analysis of events that have inadvertently favored mutations to evade vaccine effectiveness[25].
  • January 7, 2021: Added a preprint showing that some of the mutations in B.1.1.7 and 501Y.V2 increase binding affinity between the spike protein and its receptor ACE2[21].
  • January 9, 2021: Added alternate name B.1.351 for 501Y.V2[11].
  • January 20, 2021: B.1.1.7 detected in 20 US states[43]. Added L452R lineage[14][15][23].
  • January 25, 2021: Convalescent plasma often ineffective against 501Y.V2[26] and Moderna developing variant vaccine[29].
  • January 27, 2021: Mentioned D614G that became prevalent during the onset of the pandemic. See Note 1. Cited definition of lineage[3]. Mentioned epidemiological screening utility of deletions H67,V70[22]. Mentioned Brazilian variant P.1[16][17].
  • January 28, 2021: Updated evidence on B.1.1.7 mortality[33][32].
  • January 29, 2021: Cited a report by Novavax of lower vaccine effectiveness in South Africa[27], and evidence that the USA is doing far too little virus genome sequencing[40].
  • January 30, 2021: Cited Johnson & Johnson's vaccine trial results posted January 29[28].
  • February 8, 2021: Added halting of use of Astra-Zenica vaccine in South Africa[31]. Changed most mentions of 501.V2 to 501Y.V2 as this terminology seems to have become predominant.
  • February 16, 2021: Cited mutations at position 677[18]. Cited evidence for increased virulence of B.1.1.7[34].
  • February 17, 2021: Cited list of >700 defined lineages[4][9]. Used lineage nomenclature more consistently, where feasible. B.1.1.7 now in 83 countries[44].
  • March 30, 2021: Cited announcement that the UK will start variant-adapted boosters in September, 2021[30].

See Also

Notes

Note 1. The mutation D614G became predominant very early in the pandemic, before April, 2020[47]. It is not discussed above, as the purpose of this article is to show mutations that occurred months into the worldwide pandemic, after vaccine development was well underway.

References

  1. Duffy S. Why are RNA virus mutation rates so damn high? PLoS Biol. 2018 Aug 13;16(8):e3000003. doi: 10.1371/journal.pbio.3000003., eCollection 2018 Aug. PMID:30102691 doi:http://dx.doi.org/10.1371/journal.pbio.3000003
  2. Borderia AV, Rozen-Gagnon K, Vignuzzi M. Fidelity Variants and RNA Quasispecies. Curr Top Microbiol Immunol. 2016;392:303-22. doi: 10.1007/82_2015_483. PMID:26499340 doi:http://dx.doi.org/10.1007/82_2015_483
  3. 3.0 3.1 Rambaut A, Holmes EC, O'Toole A, Hill V, McCrone JT, Ruis C, du Plessis L, Pybus OG. A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology. Nat Microbiol. 2020 Nov;5(11):1403-1407. doi: 10.1038/s41564-020-0770-5. Epub, 2020 Jul 15. PMID:32669681 doi:http://dx.doi.org/10.1038/s41564-020-0770-5
  4. 4.0 4.1 4.2 4.3 4.4 PANGO Lineages, a list of more than 700 defined lineages with references where available.
  5. 5.0 5.1 Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations, a report on behalf of the COVID-19 Genomics Consortium UK (CoG-UK).
  6. 6.0 6.1 COG-UK update on SARS-CoV-2 Spike mutations of special interest. Report 1., December 20, 2020.
  7. 7.0 7.1 7.2 7.3 Investigation of novel SARS-CoV-2 variant. Variant of Concern 202012/01. Technical briefing 2. published December 28, 2020 by Public Health England.
  8. 8.0 8.1 8.2 NERVTAG/SPI-M Extraordinary meetingon SARS-CoV-2 variant of concern 202012/01 (variant B.1.1.7), December 21, 2020, from the UK Government New and Emerging Respiratory Virus Threats Advisory Group.
  9. 9.0 9.1 Tracking the international spread of SARS-CoV-2 lineages B.1.1.7 and B.1.351/501Y-V2, Áine O'Toole et al., posted January 13, 2021.
  10. 10.0 10.1 10.2 10.3 Novel variant 501.V2 with triple spike receptor binding site substit[utions posted December 21, 2020 by the GSAID Influenza and Coronavirus sequences Initiative.
  11. 11.0 11.1 11.2 Emerging SARS-CoV-2 Variants, CDC report, update of January 3, 2021.
  12. 12.0 12.1 SARS-CoV-2 UK variant: Does it matter?, a 25 min video explanation recorded December 21, 2020, by Vincent Racaniello, Professor of virology at Columbia University, New York City.
  13. 13.0 13.1 A simple chart shows why the new coronavirus variants are so worrisome, David Leonhardt, New York Times, January 4, 2021. A chart of new daily coronavirus cases shows Britain and South Africa surging, far exceeding rates in neighboring countries.
  14. 14.0 14.1 14.2 COVID-19 Variant First Found in Other Countries and States Now Seen More Frequently in California, January 17, 2021, Santa Clara County Public Health, California, USA.
  15. 15.0 15.1 15.2 Another New Covid-19 Variant Discovered In L.A. Might Be Vaccine Resistant, Researcher Says; Strain First Identified In Denmark by Tom Tapp in Deadline, January 18, 2021.
  16. 16.0 16.1 16.2 A Guide to Emerging SARS-CoV-2 Variants by Katarina Zimmer, The Scientist, January 26, 2021.
  17. 17.0 17.1 17.2 Genomic characterisation of an emergent SARS-CoV-2 lineage in Manaus: preliminary findings, Nuno R. Faria et al. on behalf of the CADDE Genomic Networ,, January 12, 2021.
  18. 18.0 18.1 Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677, a preprint by Emma B. Hodcroft et al., posted February 14, 2021.
  19. Starr TN, Greaney AJ, Hilton SK, Ellis D, Crawford KHD, Dingens AS, Navarro MJ, Bowen JE, Tortorici MA, Walls AC, King NP, Veesler D, Bloom JD. Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell. 2020 Sep 3;182(5):1295-1310.e20. doi: 10.1016/j.cell.2020.08.012. Epub 2020, Aug 11. PMID:32841599 doi:http://dx.doi.org/10.1016/j.cell.2020.08.012
  20. 20.0 20.1 Modelling conformational state dynamics and its role on infection for SARS-CoV-2 Spike protein variants, preprint posted December 17, 2020 by Teruel, Maihot & Najmanovich. Computational work suggests that N501Y increases the occupancy of the open (primed) state of the spike protein.
  21. 21.0 21.1 21.2 SARS-CoV-2 RBD in vitro evolution follows contagious mutation spread, yet generates an able infection inhibitor by Jiri Zahradnik et al., preprint posted January 6, 2020.
  22. 22.0 22.1 The SARS-CoV-2 B.1.1.7 lineage: Summary of evidence from the U.K. by Moritz Gerstung of EMBL-EBI et al., January 20, 2021.
  23. 23.0 23.1 Liu Z, VanBlargan LA, Rothlauf PW, Bloyet LM, Chen RE, Stumpf S, Zhao H, Errico JM, Theel ES, Ellebedy AH, Fremont DH, Diamond MS, Whelan SPJ. Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization. bioRxiv. 2020 Nov 8. doi: 10.1101/2020.11.06.372037. PMID:33442690 doi:http://dx.doi.org/10.1101/2020.11.06.372037
  24. 24.0 24.1 24.2 Expert reaction to the South African variant, Science Media Centre of the UK, January 4, 2021.
  25. 25.0 25.1 Musings of an anonymous, pissed off virologist by Paul Bieniasz, Professor at Rockefeller University, January 5, 2021.
  26. 26.0 26.1 SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma, preprint posted January 19, 2021.
  27. 27.0 27.1 Novavax COVID-19 Vaccine Demonstrates 89.3% Efficacy in UK Phase 3 Trial, posted January 28, 2021 by Novavax.
  28. 28.0 28.1 Johnson & Johnson Announces Single-Shot Janssen COVID-19 Vaccine Candidate Met Primary Endpoints in Interim Analysis of its Phase 3 ENSEMBLE Trial, January 29, 2021.
  29. 29.0 29.1 Moderna is designing a new version of its COVID-19 shot to fight the variant first found in South Africa by Andrew Dunn and Allison DeAngelis, Business Insider, January 25, 2021.
  30. 30.0 30.1 Exclusive: Over-70s to get booster Covid vaccines from September by Ben Riley-Smith in The Telegraph, March 26, 2021, quoting vaccines minister Nadhim Zahawi.
  31. 31.0 31.1 31.2 Covid: South Africa halts AstraZeneca vaccine rollout over new variant, BBC News, February 8, 2021.
  32. 32.0 32.1 NERVTAG note on B.1.1.7 severity, Peter Horby et al., January 18, 2021.
  33. 33.0 33.1 UK officials say people who get the contagious coronavirus variant may have a higher risk of death. Aylin Woodward for Reuters, January 25, 2021.
  34. 34.0 34.1 NERVTAG: Update note on B.1.1.7 severity, 11 February 2021.
  35. A new coronavirus strain surging to dominance in the UK appears to spread faster despite lockdowns, prompting panic and a wave of border closures, Business Insider, December 21, 2020.
  36. 36.0 36.1 France to reopen border with England for COVID-clear travellers, Reuters, December 22, 2020.
  37. 37.0 37.1 We need even tougher curbs to fight this new coronavirus strain by John Edmunds, The Guardian, December 20, 2020.
  38. 38.0 38.1 COVID-19 Genomics UK (COG-UK) Consortium, Wellcome Sanger Institute, UK.
  39. COVID-19 Genomics Consortium UK (CoG-UK).
  40. 40.0 40.1 U.S. Is Blind to Contagious New Virus Variant, Scientists Warn by Carl Zimmer, New York Times, January 6, 2021.
  41. 41.0 41.1 These are all countries that have already reported cases of the new, possibly more infectious coronavirus variant from the UK, Business Insider, December 29, 2020.
  42. 42.0 42.1 New COVID-19 Variant From U.K. Confirmed In U.S. For First Time, Huffington Post, December 29, 2020.
  43. 43.0 43.1 US COVID-19 Cases Caused by Variants, update of January 18, 2021. Centers for Disease Control and Prevention, USA.
  44. 44.0 44.1 B.1.1.7 Report, PANGO Lineages, February 17, 2021.
  45. Wrobel AG, Benton DJ, Xu P, Roustan C, Martin SR, Rosenthal PB, Skehel JJ, Gamblin SJ. SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects. Nat Struct Mol Biol. 2020 Jul 9. pii: 10.1038/s41594-020-0468-7. doi:, 10.1038/s41594-020-0468-7. PMID:32647346 doi:http://dx.doi.org/10.1038/s41594-020-0468-7
  46. South African SARS-CoV-2 Variant Alarms Scientists, Max Kozlov, The Scientist, January 5, 2021.
  47. Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W, Hengartner N, Giorgi EE, Bhattacharya T, Foley B, Hastie KM, Parker MD, Partridge DG, Evans CM, Freeman TM, de Silva TI, McDanal C, Perez LG, Tang H, Moon-Walker A, Whelan SP, LaBranche CC, Saphire EO, Montefiori DC. Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell. 2020 Aug 20;182(4):812-827.e19. doi: 10.1016/j.cell.2020.06.043. Epub 2020 , Jul 3. PMID:32697968 doi:http://dx.doi.org/10.1016/j.cell.2020.06.043

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