sars-cov-2

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Last Update: 2022

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).

3D Structural Data
References

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: B.1.1.7


WHO Label: Alpha


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

3D Structural Data
Country: SOUTH AFRICA

Lineage: B.1.351


WHO Label: Beta


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

3D Structural Data
Country: BRAZIL / JAPAN

Lineage: P.1


WHO Label: Gamma


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)

3D Structural Data
Country: INDIA

Lineage: B.1.617.2


WHO Label: Delta


3D Structural Data
Country: SOUTH AFRICA

Lineage: BA.1​, BA.5


WHO Label: Omicron


Predicted Attributes:

  • Variant 21K(Omicron) appears to have arisen in November 2021, possibly in South Africa. Early sequences are predominantly from South Africa, though also detected in Botswana and Hong Kong34
  • 21K(Omicron) is primarily of concern due to the large number of mutations it has in the Spike gene. Many of these variants are in the receptor binding domain and N-terminal domain, and thus may play key roles in ACE2 binding and antibody recognition34

3D Structural Data

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.1.427, B.1.429


WHO Label: Epsilon


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

3D Structural Data
Country: BRAZIL

Lineage: P.2 (484 K.V2)


WHO Label: Zeta


Predicted Attributes:

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

3D Structural Data
Country: USA - NY

Lineage: B.1.525


WHO Label: Eta


Predicted Attributes:

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

3D Structural Data
Country: USA - NY

Lineage: B.1.526


WHO Label: Iota


Predicted Attributes:

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

3D Structural Data
Country: INDIA

Lineage: B.1.617.1, B.1.617.3


WHO Label: Kappa


3D Structural Data

Variants under Monitoring


A SARS-CoV-2 variant with genetic changes that are suspected to affect virus characteristics with some indication that it may pose a future risk, but evidence of phenotypic or epidemiological impact is currently unclear, requiring enhanced monitoring and repeat assessment pending new evidence.​

Country: ITALY

Lineage: B.1.640.1


WHO Label: Ihu


(*) Provided by Istituto Spallanzani

Predicted Attributes:

  • Phylogeny performed also showed that B.1.640 and 'IHU variants' were most closely related between each other but comprised two divergent branches35

3D Structural Data

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



For each country, we show the main 3D model in the colored box. In addition, we show other structures with different mutations (MUTANT) in the white boxes.​

UK


Alpha α​

Lineage: B.1.1.7 

Mutations: AHV69-70Δ, Y144Δ, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H

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

MD Trajectories coming soon
Mutant 10

 

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

MD Trajectories coming soon

SOUTH AFRICA


Beta β​

Lineage: B.1.351

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

Omicron ο (1)​

Lineage: BA.1

Mutations: A67V, H69Δ, V70Δ, T95I, G142D, V143Δ, Y144Δ, Y145Δ, N211Δ, L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, L981F

Omicron ο (5)​

Lineage: BA.5

Mutations: Δ25/27, Δ69/70, G142D, V213G, G339D, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K,L452R,S477N,T478K,E484A,F486V, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, N969K

BRAZIL


Gamma γ​

Lineage: P.1

Mutations: D138Y, R190S, K417T, E484K,N501Y, D614G, H655Y, T1027I

Zeta ζ ​

Lineage: P.2 (484 K.V2)

Mutations: E484K, D614G, V1176F

Mutant 6

 

Mutations: K417N, E484K, N501Y

MD Trajectories coming soon
Mutant 7

 

Mutations: E484K

MD Trajectories coming soon
Mutant 13

 

Mutations: E484K, V1176F

MD Trajectories coming soon
Mutant 14

 

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

MD Trajectories coming soon

INDIA


Delta δ​

Lineage: B.1.617.2

Mutations: EE156/157Δ, R158G, L452R, T478K, D614G, P681R, D950N

Kappa κ ​

Lineage: B.1.617.1, B.1.617.3

Mutations: E154K, E484Q, D614G, P681R, Q1071H

USA


Epsilon ε ​

Lineage: B.1.427, B.1.429

Mutations: S13I, W152C, L452R, D614G

Eta η ​

Lineage: B.1.525

Mutations: Q52R, A67V, Δ69/70, Δ144/144, E484K, D614G, Q677H, F888L

Iota ι (1) ​

Lineage: B.1.526

Mutations: L5F, T95I, D253G, S477N, D614G

Iota ι (2) ​

Lineage: B.1.526

Mutations: L5F, T95I, D253G, E484K, D614G

ITALY


Ihu ​

Lineage: B.1.640.1

Mutations: E96Q, CNDPFLGVY136-144Δ, R190S, I210T, R346S, N394S, Y449N, F490R, N501Y, D614G, P681H, T859N, D936H, K1191N

Models built based on PDB 6VYB returned to its wild-type form and fully glycosylated,
thanks to Universitá della Tuscia, DIBAF Department,
thanks to The Department of Biotechnology of the High Institute of Biotechnology of Sidi Thabet (University of Manouba, Tunisia)
thanks to The Laboratory of Transmissible Diseases and Biological Active Substances LR99ES27, Faculty of Pharmacy (University of Monastir, Tunisia).

Models built based on heteromer PDB 7A94 SPIKE with ACE2_HUMAN bound,
thanks to Swiss intitute of Bioinformatics.

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 

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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)  

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34. https://covariants.org/variants/21K.Omicron​

35. https://www.medrxiv.org/content/10.1101/2021.12.24.21268174v1.full.pdf

36. The resulting protein structure of spike glycoprotein WT and mutants were glycosylated following the protocol described in Borocci et al.
[doi:10.3390/ijms22115464]


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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