SARS-CoV-2 Variants

B.1.1.7 Lineage of SARS-CoV-2

[Rambaut et al, 2020]

In September of 2020 a new lineage of SARS-CoV-2, known as B.1.1.7, was discovered in the United Kingdom (newly designated by WHO as Alpha). This lineage was found to have developed 14 lineage-specific amino acid replacements and 3 deletions prior to its discovery. It appears that the B.1.1.7 is now evolving at a rate similar to other SARS-CoV-2 lineages which have a rate of mutation of about one to two mutations per month (Duchene et al. 2020).

One of the mutations associated with this lineage is a N501Y in the spike protein of the virus. It is believed that this mutation is able to increase the spike protein's affinity for the host ACE2 receptor (Starr et al. 2020) and it has been associated with increased infectivity and virulence (Gu et al. 2020). B.1.1.7 viruses have also been shown to have a P681H mutation in the cleavage site of the spike protein. This location is one of the residues that make up the furin cleavage site between S1 and S2 in spike. The S1/S2 furin cleavage site has been shown in animal models to promote viral entry into respiratory epithelial cells and transmission (Hoffmann et al. 2020; Peacock et al. 2020; Zhu et al. 2020). The spike proteins of this lineage have also been shown to have a deletion at amino acids 69-70. This mutation in the receptor-binding domain of spike is a recurrent deletion that has been found in various lineages associated with SARS-CoV-2 (McCarthy et al. 2020; Kemp et al. 2020). Outside of spike, a Q27 stop mutation truncates the ORF8 protein of the virus, rendering the protein inactive. An ORF8 deletion at amino acid 382 has a mild effect on virus replication in human airway cells (Gamage et al. 2020). The B.1.1.7. lineage also has five synonymous mutations in ORF1ab and one synonymous mutation in the M gene.

COVID-19 Alpha Variant (B.1.1.7) Specific Antibodies

ProSci Incorporated is a proud contributor to this scientific research by having antibody reagents available at the time of the outbreak. The use of the ProSci Spike Antibody (Cat. No. 3525) has been cited in numerous publications in 2020 and 2021. Of great interest now, while ProSci offers antibodies and recombinant proteins representing the full SARS-CoV-2 proteome, and host factors, today we announce the availability of Spike S1 Antibodies to variant SARS-CoV-2 B.1.1.7 (Alpha) to the P681H point mutation (Cat. No. 9359) – this residue is adjacent to the Furin cleavage site, required for viral cell entry.

Data thus far points to this SARS-CoV-2 variation offering a selective advantage to the virus and becoming globally prevalent. ProSci offers this antibody as an important reagent to help further understanding the viral mode of infection and life cycle.

ProductCat. No.WTAlpha Variant | B.1.1.7 (U.K.)Beta Variant | B.1.135 (South Africa)Gamma Variant | P.1 (Brazil)Comments
SARS-CoV-2 UK Variant (B.1.1.7) Spike P681H Antibody 9359 - ++++ N/A N/A 9359 detects Alpha Variant but not WT
SARS-CoV-2 (COVID-19) Spike S1 Antibody 9083 ++++ ++++ ++++ - 9083 cannot detect Gamma Variant
SARS-CoV-2 (COVID-19) Spike S1 Antibody [SP185] 10-351 ++++ ++++ - - 10-351 cannot detect Beta and Gamma Variants
SARS-CoV-2 (COVID-19) Spike S1 Antibody [SP422] 10-350 ++++ ++++ ++ ++ 10-350 has a lower affinity for Beta and Gamma Variants
SARS-CoV-2 (COVID-19) Spike RBD Antibody 9087 ++++ +++ ++ + 9087 has a lower affinity for all variants
SARS-CoV-2 (COVID-19) Spike S1 Antibody (cleavage) 9091 ++++ ++ N/A N/A 9091 has a lower affinity for Alpha Variant
ProductCat. No.ApplicationClonalitySpecies
SARS-CoV-2 UK Variant (B.1.1.7) Spike P681H Antibody 9359 E, WB Polyclonal Rabbit
SARS-CoV-2 (COVID-19) Spike S1 Antibody 9083 E, WB, IF, IHC Polyclonal Rabbit
SARS-CoV-2 (COVID-19) Spike S1 Antibody [SP185] 10-351 E, IHC Monoclonal Rabbit
SARS-CoV-2 (COVID-19) Spike S1 Antibody [SP422] 10-350 E, IHC Monoclonal Rabbit
SARS-CoV-2 (COVID-19) Spike RBD Antibody 9087 E, WB, IF, IHC Polyclonal Rabbit
SARS-CoV-2 (COVID-19) Spike S1 Antibody (cleavage) 9091 E, WB, IF Polyclonal Rabbit

Variant Recombinant Proteins

ProductCat. No.VariantMutationsSource
SARS-CoV-2 (COVID-19) S RBD (N501Y) Protein 11-064 Alpha | 501Y.V1 N501Y Mammalian
SARS-CoV-2 (COVID-19) S RBD (K417N, E48K, N501Y) Protein 11-065 Beta | 501Y.V2 K417N, E484K, N501Y Mammalian Cells
SARS-CoV-2 (COVID-19) S RBD (E484K, K417T, N501Y) Protein 11-066 Gamma | 501Y.V3 E484K, K417T, N501Y Mammalian Cells
SARS-CoV-2 (COVID-19) S RBD (E484K) Protein 11-067 501Y.V2/V3 E484K Mammalian
SARS-CoV-2 (COVID-19) Spike (D614G) Trimer Protein 92-748 501Y.V2 D614G Human Cells
SARS-CoV-2 (COVID-19) Spike (D614G) S1 Protein 92-746 501Y.V2 D614G Human Cells


Non-synonymous mutations and deletions of B.1.1.7 lineage.

GeneNucleotideAmino AcidProteinRelated ProSci AbsAb ImmunogenBiological Significance
Spike 21765-21770 deletion HV 69-70 deletion (S1-NT) Recurrent deletions in various lineages related to several RBD mutations
A23063T N501Y RBD 9087 Mutation site included An increase in the binding affinity of ACE2 receptor and enhance infectivity and virulence
C23604A P681H S1-CT 9359 Mutation site included Promote viral entry into human cells and transmission in animal models
21991-21993 Y144 deletion S1
C23271A A570D S1
C23709T T716I S2-NT
T24506G S982A S2'
G24914C D1118H S2'
ORF1ab C3267T T1001I NSP3/PL-PRO
C5388A A1708D NSP3/PL-PRO
T6954C I2230T NSP3/PL-PRO
11288-11296 deletion SGF 3675-3677 deletion NSP6
ORF8 C27972T Q27stop ORF8-NT A slight effect on virus replication in human cells with deletions
G28048T R52I ORF8 Incoming ORF8 Ab Mutation site included
A28111G Y73C ORF8 10-511 Mutation site included
N 28280 GAT-CTA D3L N-NT 35-579 Mutation site included
C28977T S235F N

[Edited from Rambaut et al, 2020]


SARS-CoV-2 Spike Recombinant Proteins (D614G)

ProductCat. No.SourceFusion TagSequence
SARS-CoV-2 (COVID-19) S-Trimer Protein Recombinant Protein (D614G) 92-748 Human Cells C-6 His Tag Cys15 - Gln1208 (D614G)
SARS-CoV-2 (COVID-19) S1 Protein Recombinant Protein (D614G) 92-746 Human Cells C-10 His Tag Gln14 - Arg685 (D614G)


SARS-CoV-2 (COVID-19) S RBD Mutant Recombinant Proteins

ProductCat. No.SourceFusion TagSequence
SARS-CoV-2 (COVID-19) Spike RBD Recombinant Protein 92-750 Human Cells C-6His Tag Arg319 - Phe541 (F342L)
SARS-CoV-2 (COVID-19) Spike RBD Recombinant Protein 92-751 Human Cells C-6His Tag Arg319 - Phe541 (N354D)
SARS-CoV-2 (COVID-19) Spike RBD Recombinant Protein 92-752 Human Cells C-6His Tag Arg319 - Phe541 (V367F)
SARS-CoV-2 (COVID-19) Spike RBD Recombinant Protein 92-753 Human Cells C-6His Tag Arg319 - Phe541 (R408I)
SARS-CoV-2 (COVID-19) Spike RBD Recombinant Protein 92-754 Human Cells C-6His Tag Arg319 - Phe541 (A435S)
SARS-CoV-2 (COVID-19) Spike RBD Recombinant Protein 92-755 Human Cells C-6His Tag Arg319 - Phe541 (K458R)
SARS-CoV-2 (COVID-19) Spike RBD Recombinant Protein 92-756 Human Cells C-6His Tag Arg319 - Phe541 (G476S)
SARS-CoV-2 (COVID-19) Spike RBD Recombinant Protein 92-757 Human Cells C-6His Tag Arg319 - Phe541 (V483A)
SARS-CoV-2 (COVID-19) Spike RBD Recombinant Protein 92-758 Human Cells C-6His Tag Arg319 - Phe541 (D364Y)
SARS-CoV-2 (COVID-19) Spike RBD Recombinant Protein 92-759 Human Cells C-6His Tag Arg319 - Phe541 (V341I)
SARS-CoV-2 (COVID-19) S RBD-SD1 Recombinant Protein (V367F) 92-742 Human Cells C-6 His Tag Arg319 - Ser591 (V367F)
SARS-CoV-2 (COVID-19) Spike RBD-SD1 Recombinant Protein (N354D, D364Y) 92-743 Human Cells C-6His Tag Arg319 - Ser591 (N354D, D364Y)
SARS-CoV-2 (COVID-19) Spike RBD-SD1 Recombinant Protein (W436R) 92-744 Human Cells C-6His Tag Arg319 - Ser591 (W436R)


SARS-CoV-2 (COVID-19) Virus Antibody Research

ProSci Incorporated has developed and manufactured SARS-CoV-2 (COVID-19, 2019-nCoV) antibodies, antigens, and other reagents related to cellular entry: ACE2 receptor, TMPRSS2, and furin enzyme. ProSci Inc. is continuously adding new SARS-CoV-2 reagents for Spike, S1, S2, nucleocapsid, membrane, envelope including llama single-domain antibodies and recombinant proteins.


References

  • Duchene, Sebastian, Leo Featherstone, Melina Haritopoulou-Sinanidou, Andrew Rambaut, Philippe Lemey, and Guy Baele. 2020. “Temporal Signal and the Phylodynamic Threshold of SARS-CoV-2.” Virus Evolution 6 (2): veaa061.
  • Gamage, Akshamal M., Kai Sen Tan, Wharton O. Y. Chan, Jing Liu, Chee Wah Tan, Yew Kwang Ong, Mark Thong, et al. 2020. “Infection of Human Nasal Epithelial Cells with SARS-CoV-2 and a 382-Nt Deletion Isolate Lacking ORF8 Reveals Similar Viral Kinetics and Host Transcriptional Profiles.” PLoS Pathogens 16 (12): e1009130.
  • Gu, Hongjing, Qi Chen, Guan Yang, Lei He, Hang Fan, Yong-Qiang Deng, Yanxiao Wang, et al. 2020. “Adaptation of SARS-CoV-2 in BALB/c Mice for Testing Vaccine Efficacy.” Science 369 (6511): 1603–7.
  • Hoffmann, Markus, Hannah Kleine-Weber, and Stefan Pöhlmann. 2020. “A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells.” Molecular Cell 78 (4): 779–84.e5.
  • Kemp, S. A., D. A. Collier, R. Datir, S. Gayed, A. Jahun, M. Hosmillo, Iatm Ferreira, et al. 2020. “Neutralising Antibodies Drive Spike Mediated SARS-CoV-2 Evasion.” Infectious Diseases (except HIV/AIDS). medRxiv. https://doi.org/10.1101/2020.12.05.20241927.
  • McCarthy, Kevin R., Linda J. Rennick, Sham Nambulli, Lindsey R. Robinson-McCarthy, William G. Bain, Ghady Haidar, and W. Paul Duprex. 2020. “Natural Deletions in the SARS-CoV-2 Spike Glycoprotein Drive Antibody Escape.” Microbiology. bioRxiv.
  • Peacock, Thomas P., Daniel H. Goldhill, Jie Zhou, Laury Baillon, Rebecca Frise, Olivia C. Swann, Ruthiran Kugathasan, et al. 2020. “The Furin Cleavage Site of SARS-CoV-2 Spike Protein Is a Key Determinant for Transmission due to Enhanced Replication in Airway Cells.” Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.09.30.318311.
  • Starr, Tyler N., Allison J. Greaney, Sarah K. Hilton, Daniel Ellis, Katharine H. D. Crawford, Adam S. Dingens, Mary Jane Navarro, et al. 2020. “Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding.” Cell 182 (5): 1295–1310.e20.
  • Zhu, Yunkai, Fei Feng, Gaowei Hu, Yuyan Wang, Yin Yu, Yuanfei Zhu, Wei Xu, et al. 2020. “The S1/S2 Boundary of SARS-CoV-2 Spike Protein Modulates Cell Entry Pathways and Transmission.” Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.08.25.266775.