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SARS-CoV-2 (COVID-19) Spike Variant Recombinant Proteins

28-Jun-2021

There are multiple SARS-CoV-2 variants currently spreading across the planet, with four of them being designated “Variants of Concern” (VOC) by the World Health Organization (WHO). Several nomenclature systems for these variants exist, and the Greek alphabet designation introduced by WHO is the latest (Table 1). All four of these viruses have mutations (~seventeen to twenty-three) at different points in their genomes, with eight to eleven of these alterations occurring in their respective spike proteins (all have D614G, Figure 1). At this point, most experts think the present vaccines will have efficacy against these variants though there is some unease among scientists and physicians about increased transmissibility and virulence, particularly in regions with low vaccination rates. As the greatest interest has focused on the spike mutations, we offer the following images to illustrate their location in these genomes.

WHO label   Pango lineage   GISAID clade/lineage   Nextstrain clade   Earliest documented samples
Alpha   B.1.1.7   GRY (formerly GR/501Y.V1)   20I/S:501Y.V1   United Kingdom
Beta   B.1.351   GH/501Y.V2   20H/S:501Y.V2   South Africa
Gamma   P.1   GR/501Y.V3   20J/S:501Y.V3   Brazil
Delta   B.1.617.2   G/452R.V3   21A/S:478K   India

 

Table 1. VOC Nomenclature

 

Sars-cov-2 (COVID-19) spike mutant sites

Figure 1. Identified Mutations in VOC Spike Proteins

 

Mutation Site
  Characteristics   Variant of Concern  
References
D614G  

D614G is now ubiquitous and alters spike conformation as well as enhancing furin cleavage and ACE2 affinity. It also is linked to higher virus infectivity.

 

Alpha, Beta, Gamma, Delta

  1,2
N501Y  

N501Y increases the affinity of spike for cell receptors, which facilitates viral transmission. It was shown to bestow the greatest enhancement of ACE2 affinity for any single RBD mutation. It may also disrupt binding of some antibodies.

 

Alpha, Beta, Gamma

  3,4,5,7
E484K  

E484K appears to be involved in immune evasion of some monoclonal antibody therapies and potentially diminishes the vaccine response. There is concern that this mutation may elevate risk of reinfection. Changes at E484 to K, Q, or P result in more than an order of magnitude change in neutralization titers of convalescent plasma.

 

Alpha (present in certain sequences), Beta, Gamma

  3,4,5,7
K417N  

K417N may result in lower binding affinity of spike for ACE2, but it also is involved in immune evasion of certain monoclonal antibody therapies. It affects class 1 antibody binding.

  Beta   3,4,5,7
K417T  

K417T activity is similar to K417N (see above).

  Gamma   3,4,5
L452R  

L452R decreases neutralization by some monoclonal antibodies  and convalescent plasma. Its occurrence in other variants found around the world suggests it is an adaptation to increasing immunity.

  Delta   5
T478K  

T478K increases the electrostatic potential of spike's receptor binding domain that interacts with ACE2, potentially making variants with this mutation more transmissible and more infectious.

  Delta   6,7
S494P  

S494P enhances ACE2 binding and appears to confer increased immune evasion.

 

Alpha (present in certain sequences)

  7

 

Table 2. Key VOC Spike Protein Mutations

 

B.1.1.7 (SARS-CoV-2 Alpha)

In late 2020, the United Kingdom reported the B.1.1.7 variant (aka Alpha) that appears to be significantly more transmissible and perhaps more virulent. Eight of its twenty-three mutations are in the spike protein, with N501Y in the receptor binding domain (RBD) being of most concern as it may be involved in increased ACE2 affinity.

 

B.1.351 (SARS-CoV-2 Beta)

In January of 2021, the B.1.351 variant (aka Beta) was found in South Africa. It has twenty-one mutations, with eight being in the spike protein. As with the other two variants, it includes the N501Y mutation but also has two additional RBD mutations (E484K, K417N). It appears to be more transmissible, and the E484K mutation is worrisome as it was shown to reduce antibody recognition.

 

P.1 (SARS-CoV-2 Gamma)

Near the end of January 2021, Japanese authorities reported a new SARS-CoV-2 virus variant obtained from four Brazilian travelers. This variant is designated P.1 (aka Gamma) and has seventeen mutations, with eleven in spike. Some evidence suggests that this virus may also be more transmissible and have some immune escape capability. It has mutations at the same three RBD residues that are altered in the Beta genome.

 

B.1.617.2 (SARS-CoV-2 Delta)

B.1.617 was first detected in Maharashtra, India in December 2020. There are three sublineages categorized, with B.1.617.2/Delta being designated a VOC due to reports that it is now dominant in many countries, including India and the UK. The B.1.617.2 variant carries ten mutations in spike protein and may be more resistant to neutralization by vaccines and certain monoclonal antibody therapies.

GeneTex is now developing reagents to support research into these SARS-CoV-2 variants, beginning with recombinant spike/RBD proteins that include many of these key mutations.

 

See All Reagents

 

Recombinant Proteins
 

Wild-type and Single Mutation Spike Protein

Product Name Expression System   Cat. No.
Spike (ECD) protein, His tag (active) HEK293   GTX135972-pro
Spike RBD protein, His tag (active) HEK293   GTX136090-pro
Spike S1 protein, His tag (active) HEK293   GTX135817-pro
Spike S2 (ECD) protein, mouse IgG Fc tag HEK293   GTX135684-pro
Spike (D614G Mutant) protein (ECD), His tag (active) HEK293   GTX02575-pro

 

B.1.1.7 (Alpha) Spike Proteins

Product Name Expression System   Cat. No.
Spike (del69-70, del144, N501Y, A570D, D614G, P681H,T716I, S982A, D1118H) (ECD) Protein, His tag (active) HEK293   GTX136059-pro
Spike RBD (N501Y Mutant) protein, His tag (active) HEK293   GTX136014-pro
Spike RBD (E484K, N501Y Mutant) protein, His tag (active) HEK293   GTX136058-pro
Spike S1 (del69-70, del144, N501Y, A570D, D614G, P681H Mutant) protein, His tag HEK293   GTX136085-pro
Spike S2 (T716I, S982A, D1118H Mutant) (ECD) protein, His tag HEK293   GTX136023-pro

 

B.1.351 (Beta) Spike Proteins

Product Name Expression System   Cat. No.
Spike (L18F,..., K417N, E484K, N501Y,...)(ECD) Protein, His tag (active) HEK293   GTX136061-pro
Spike RBD (K417N, E484K, N501Y Mutant) protein, His tag (active) HEK293   GTX136022-pro
Spike S1 (L18F, D80A, D215G, R246I, K417N, E484K, N501Y, D614G Mutant) protein, His tag HEK293   GTX136095-pro

 

P.1 (Gamma) Spike Proteins

Product Name Expression System   Cat. No.
Spike (L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, V1176F Mutant) (ECD) protein, His tag HEK293   GTX136091-pro
Spike RBD (K417T, E484K, N501Y Mutant) protein, His tag (active) HEK293   GTX136043-pro
Spike S1 (L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G Mutant) protein, His tag HEK293   GTX136094-pro

 

B.1.617.2 (Delta) Spike Proteins

Product Name Expression System   Cat. No.
Spike RBD (L452R, T478K Mutant) protein, His tag (active) HEK293  

GTX136332-pro

SARS-CoV-2 (COVID-19) Spike RBD Protein, AY.1 / Delta plus variant, His tag HEK293  

GTX136333-pro

 

References

  1. Cell Rep. 2021 Jan 12;34(2):108630.
  2. Nat Commun. 2021 Feb 8;12(1):848.
  3. Cell. 2020 Sep 3;182(5):1295-1310.e20.
  4. J Cell Physiol. 2021 Mar 23.
  5. Nat Rev Microbiol. 2021 Jul;19(7):409-424.
  6. J Med Virol. 2021:1-6.
  7. Genomics. 2021;113:2158-2170.