sars-cov-2

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Last Update: July 2021

Sars-CoV-2 SPIKE Variants

Covid-19 is changing: the emerging variants involving the protein sequence of the Sars-CoV-2 Spike protein are now our fear. But how do they act? Exscalate4CoV tries to answer this difficult question with the Spike Mutants project.
The Spike Mutants website aims to provide the scientific community with structural information on emerging variants involving the protein sequence of the Sars-CoV-2 Spike protein.

All viruses, including SARS-CoV-2, change over time. Some changes may affect the virus’s properties, such as how easily it spreads, the associated disease severity, or the performance of vaccines, therapeutic medicines, diagnostic tools, or other public health and social measures.  WHO, in collaboration with partners, expert networks, national authorities, institutions and researchers have been monitoring and assessing the evolution of SARS-CoV-2 since January 2020. During late 2020, the emergence of variants that posed an increased risk to global public health prompted the characterisation of specific Variants of Interest (VOIs) and Variants of Concern (VOCs). (www.who.int).

Variants of Concern


A variant for which there is evidence of an increase in transmissibility, more severe disease (increased hospitalizations or deaths), significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.

Country: UK

Lineage: 20I/501Y.V1 (B.1.1.7 lineage)1-3


WHO Label: Alpha


Mutations: Δ69/70, Δ144Y, E484K*, S494P*, N501Y, A570D, D614G, P681H, T716I, S982A, and D1118H

(*)=detected in some sequences but not all

Predicted Attributes:

  • ~50% increased transmission18
  • Minimal impact on neutralization by Emergency Use Authorization (EUA) monoclonal antibody therapeutics20,21
  • Minimal impact on neutralization by convalescent and post-vaccination sera22-28
Country: SOUTH AFRICA

Lineage: B.1.351(20H/501.V2) or 501Y.V2 (B.1.351 lineage)3-7,17


WHO Label: Beta


Mutations: L18F*, D80A*, D215G*, R246I*, K417N, E484K, N501Y, D614G and A701V*, Del241-243* or Del242-244*

(*)=detected in some sequences but not all

Predicted Attributes:

  • ~50% increased transmission30
  • Moderate impact on neutralization by EUA monoclonal antibody therapeutics20,21
  • Moderate reduction on neutralization by convalescent and post-vaccination sera22,26,28,31,32
Country: BRAZIL / JAPAN

Lineage: P.1 (20J/501Y.V3) B.1.1.248;
This variant likely arose from the Amazonas region of Brazil8-13


WHO Label: Gamma


Mutations: LL18F, T20N, P26S, D138Y, R190S*, K417N/T, E484K, N501Y, D614G, H655Y, T1027I, V1176F

(*)=detected in some sequences but not all

Predicted Attributes:

  • Moderate impact on neutralization by EUA monoclonal antibody therapeutics20,21
  • Reduced neutralization by convalescent and postvaccination sera29
  • May have enhanced transmissibility like the South African variant as they share a similar pattern of mutations (N501Y, E484K, K417N/T)
Country: INDIA

Lineage: B.1.617.2


WHO Label: Delta


Mutations: L452R, E484Q and P681R, ΔE156, ΔF157


Variants of Interest


A variant with specific genetic markers that have been associated with changes to receptor binding, reduced neutralization by antibodies generated against previous infection or vaccination, reduced efficacy of treatments, potential diagnostic impact, or predicted increase in transmissibility or disease severity

Country: US - CALIFORNIA

Lineage: B.1.429 (20C/S:452R or CAL.20C)


WHO Label: Epsilon


Mutations: S13I, W152C, L452R, D614G

Predicted Attributes:

  • ~20% increased transmissibility33
  • Significant impact on neutralization by some, but not all, EUA therapeutics
  • Moderate reduction in neutralization using convalescent and post-vaccination sera 33
Country: BRAZIL

Lineage: P.2 (484 K.V2)11


WHO Label: Zeta


Mutations: E484K, D614G, V1176F

Predicted Attributes:

  • Potential reduction in neutralization by monoclonal antibody treatments
  • Potential reduction in neutralization by convalescent and post-vaccination sera
Country: USA - NY

Lineage: B.1.525 (20A/S:484K)


WHO Label: Eta


Mutations: A67V, Δ69/70, Δ144, E484K, D614G, Q677H, F888L

Predicted Attributes:

  • Potential reduction in neutralization by monoclonal antibody treatments
  • Potential reduction in neutralization by convalescent and post-vaccination sera
Country: USA - NY

Lineage: B.1.526(20C/S:484K)14


WHO Label: Iota


Mutations: L5F, T95I, D253G, (either S477N or E484K)*, D614G, A701V

Predicted Attributes:

  • Potential reduction in neutralization by monoclonal antibody treatments
  • Potential reduction in neutralization by convalescent and post-vaccination sera
Country: INDIA

Lineage: B.1.617.1, B.1.617.3


WHO Label: Kappa


Mutations: L452R, E484Q, and P681R

Country: VIETNAM

Lineage: -


WHO Label: -


Mutations: A222V, D614G, D950N, E156G, ΔF157/ΔR158, G142D, L452R, P681R, T19R, T478K, ΔY144*

(*)=detected in some sequences but not all

Predicted Attributes:

  • None information yet

COVID-19 in VR: Spike Protein Mink Mutations

In this video we discuss the amino acid changes in the spike surface glycoprotein that appeared during the recent outbreak in Danish mink and their effect on the antigenicity of the SARS-CoV-2 virus.

Spike Protein Mink Mutations

3D Structural Data



UK


Mutant 1*

Mutations: AHV 69-70Δ, Y144 Δ, N501Y, D614G, P681H. This mutant is for UK variant

Mutant 2*

Mutations: HV 69-70Δ, Y144 Δ, N501Y, P681H. This mutant is for UK variant without D614G

Mutant 9**

Mutations: HV69-70Δ, Y144Δ, N501Y, D614G, P681H


Mutant 10**

Mutations: HV69-70Δ, Y144Δ, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H

SOUTH AFRICA


Mutant 11**

Mutations: L18F, D80A, D215G, R246I, K417N, E484K, N501Y, D614G, A701V, Δ241-243

BRAZIL


Mutant 3*

Mutations:K417N, E484K, N501Y

Mutant 4*

Mutations:E484K

Mutant 6**

Mutations:K417N, E484K, N501Y

Mutant 7**

Mutations:E484K

Mutant 13**

Mutations:E484K, V1176F

Mutant 14**

Mutations:L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, V1176F

INDIA


Mutant 16*

Mutations:L452R, E484Q, P681R

Mutant 17*

Mutations:L452R, P681R

USA


Mutant 15*

Mutations:S13I, W152C, L452R, D614G

VIETNAM


Mutant 18*

Mutations:A222V, D614G, D950N, E156G, ΔF157/ΔR158, G142D, L452R, P681R, T19R, T478K, ΔY144* NOT GLYCOSILATED

REFERENCES

1. Andrew Rambaut, Nick Loman, Oliver Pybus, Wendy Barclay, Jeff Barrett, Alesandro Carabelli, Tom Connor, Tom Peacock, David L Robertson, Erik Volz, on behalf of COVID-19 Genomics Consortium UK (CoG-UK). Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations. https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563. 

2. WHO SARS-CoV-2 variant—United Kingdom of Great Britain and Northern Ireland.
https://www.who.int/csr/don/21-december-2020-sars-cov2-variant-united-kingdom/en 

3. European Centre for Disease Prevention and Control. Risk related to spread of new SARS-CoV-2 variants of concern in the EU/EEA –29 December2020. ECDC: Stockholm; 2020. https://www.ecdc.europa.eu/sites/default/files/documents/COVID-19-risk-related-to-spread-of-new-SARS-CoV-2-variants-EU-EEA.pdf 

4. Tegally H, Wilkinson E, Giovanetti M, Iranzadeh A, Fonseca V,Giandhari J, et al. Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. medRxiv [Preprint]. 22 December 2020; Available from: https://www.medrxiv.org/content/10.1101/2020.12.21.20248640v151.Salim S. 

5. Abdool Karim. The 2nd Covid-19 wave in South Africa:Transmissibility & a 501.V2 variant. 18 December 2020. Available from: https://www.scribd.com/document/488618010/Full-Presentation-by-SSAK-18-Dec 

6. Republic of South Africa -Department of Health. Update on Covid-19.18 December 2020. Available from: https://sacoronavirus.co.za/2020/12/18/update-on-covid-19-18th-december-2020/ 

7. Houriiyah Tegally et al. Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. medRxiv 2020.12.21.20248640; doi: https://doi.org/10.1101/2020.12.21.20248640 

8. Paola Cristina Resende et al. Spike E484K mutation in the first SARS-CoV-2 reinfection case confirmed in Brazil, 2020. https://virological.org/t/spike-e484k-mutation-in-the-first-sars-cov-2-reinfection-case-confirmed-in-brazil-2020/584. 

9. Felipe Naveca et al. Phylogenetic relationship of SARS-CoV-2 sequences from Amazonas with emerging Brazilian variants harboring mutations E484K and N501Y in the Spike protein. https://virological.org/t/phylogenetic-relationship-of-sars-cov-2-sequences-from-amazonas-with-emerging-brazilian-variants-harboring-mutations-e484k-and-n501y-in-the-spike-protein/585 

10. Nuno R. Faria et al. Genomic characterisation of an emergent SARS-CoV-2 lineage in Manaus: preliminary findings. https://virological.org/t/genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-manaus-preliminary-findings/586 

11. Naveca F., Nascimentio V., Souza V., et al. Phylogenetic relationship of SARS-CoV-2 sequences from Amazonas with emerging Brazilian variants harboring mutations E484K and N501Y in the Spike protein. 11 January 2021. https://virological.org/t/phylogenetic-relationship-of-sars-cov-2-sequences-from-amazonas-with-emerging-brazilian-variants-harboring-mutations-e484k-and-n501y-in-the-spike-protein/58. (Accessed 18th January 2021)  

12. Brief report: New Variant Strain of SARS-CoV-2Identified in Travelers from Brazil. https://www.niid.go.jp/niid/images/epi/corona/covid19-33-en-210112.pdf

13. Hirotsu, Y., & Omata, M. (2021). Discovery of a SARS-CoV-2 variant 1 from the P.1 lineage harboring K417T/E484K/N501Y mutations in Kofu, Japan. The Journal of infection, S0163-4453(21)00130-4. Advance online publication. https://doi.org/10.1016/j.jinf.2021.03.013

14. Zhou, H., Dcosta, B. M., Samanovic, M. I., Mulligan, M. J., Landau, N. R., & Tada, T. (2021). B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies. bioRxiv : the preprint server for biology, 2021.03.24.436620. https://doi.org/10.1101/2021.03.24.436620

15. Voloch C.M., da Silva F Jr R., de Almeida L.G.P., et al. Genomic characterization of a novel SARS-CoV-2 lineage from Rio de Janeiro, Brazil. 2020. medRxiv 2020.12.23.20248598; doi: https://doi.org/ 10.1101/2020.12.23.20248598

16. Toovey, O., Harvey, K. N., Bird, P. W., & Tang, J. (2021). Introduction of Brazilian SARS-CoV-2 484K.V2 related variants into the UK. The Journal of infection, S0163-4453(21)00047-5. Advance online publication. https://doi.org/10.1016/j.jinf.2021.01.025

17. Tegally, H., Wilkinson, E., Giovanetti, M. et al. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature (2021). https://doi.org/10.1038/s41586-021-03402-9

18. Davies NG, Abbott S, Barnard RC, et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. MedRXiv 2021. doi: https://doi.org/10.1101/2020.12.24.20248822

19. Horby P, Huntley C, Davies N et al. NERVTAG note on B.1.1.7 severity. New & Emerging Threats Advisory Group, Jan. 21, 2021. Retrieved from NERVTAG note on variant severity

20. Fact Sheet For Health Care Providers Emergency Use Authorization (Eua) Of Bamlanivimab And Etesevimab 02092021 (fda.gov)

21. FACT SHEET FOR HEALTH CARE PROVIDERS EMERGENCY USE AUTHORIZATION (EUA) OF REGEN-COV (fda.gov)

22. Wang P, Nair MS, Liu L, et al. Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7. BioXRiv 2021. doi: https://doi.org/10.1101/2021.01.25.428137

23. Shen X, Tang H, McDanal C, et al. SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral Spike vaccines. BioRxiv 2021.  doi:  https://doi.org/10.1101/2021.01.27.428516

24. Edara VV, Floyd K, Lai L, et al. Infection and mRNA-1273 vaccine antibodies neutralize SARS-CoV-2 UK variant. MedRxiv 2021. doi: https://doi.org/10.1101/2021.02.02.21250799

25. Collier DA, DeMarco A, Ferreira I, et al. SARS-CoV-2 B.1.1.7 sensitivity to mRNA vaccine-elicited, convalescent and monoclonal antibodies. MedRxiv 2021. doi: https://doi.org/10.1101/2021.01.19.21249840

26. Wu K, Werner AP, Moliva JI, et al. mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. BioRxiv 2021. doi: https://doi.org/10.1101/2021.01.25.427948

27. Emary KRW, Golubchik T, Aley PK, et al. Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 VOC 202012/01 (B.1.1.7). 2021. The Lancet. doi:  http://dx.doi.org/10.2139/ssrn.3779160

28. Novavax COVID-19 Vaccine Demonstrates 89.3% Efficacy in UK Phase 3 Trial | Novavax Inc. – IR Site

29. Wang P, Wang M, Yu J, et al. Increased Resistance of SARS-CoV-2 Variant P.1 to Antibody Neutralization. BioRxiv 2021.  doi: https://doi.org/10.1101/2021.03.01.433466

30. Pearson CAB, Russell TW, Davies NG, et al. Estimates of severity and transmissibility of novel South Africa SARS-CoV-2 variant 501Y.V2.

31. Madhi SA, Ballie V, Cutland CL, et al. Safety and efficacy of the ChAdOx1 nCoV-19 (AZD1222) Covid-19 vaccine against the B.1.351 variant in South Africa. MedRxiv 2021. doi: https://doi.org/10.1101/2021.02.10.21251247

32. Johnson & Johnson COVID-19 Vaccine Authorized by U.S. FDA For Emergency Use | Johnson & Johnson (jnj.com)

33. Deng X, Garcia-Knight MA, Khalid MM, et al. Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation. MedRxiv 2021. doi: https://doi.org/10.1101/2021.03.07.21252647


We acknowledge ENI and CINECA
for the support and concession of the HPC5 and Marconi100 super-computers,
indispensable high-performance processing resources for the molecular dynamics experiments.

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developed by Anna Fava for Nuovi S.O.C.I.