Proteins for Coronavirus Research

Proteins for Coronavirus Research

Coronavirus Proteins

Now available! B.1.1.7 Variant Spike RBD Protein (N501Y)

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R&D Systems offers a range of SARS-CoV-2 proteins and other Coronavirus proteins with the same industry-leading quality specifications as our other recombinant proteins. Our SARS-CoV-2 Spike proteins exhibit high affinity binding to human ACE-2 in both ELISA and SPR. And the Coronavirus proteases, Papain-like Protease and 3CL protease, are tested for bioactivity using biologically relevant fluorescent substrates. For more detailed information about our recombinant Coronavirus proteins, visit the product pages listed below.

NEW Application Note: Glycosylation of the receptor binding domain of COVID-19 virus spike protein

View frequently asked questions about our coronavirus proteins.

Coronavirus Proteins

Spike Protein

New SARS-CoV-2 Spike Protein Variants

R&D Systems is quickly developing new SARS-CoV-2 protein mutants as they are identified. The first B.1.1.7 Spike protein mutants are available to order as we continue to develop a comprehensive set of Spike protein mutants to the latest SARS-CoV-2 variants B.1.1.7, B.1.351, and P.1. View our available Spike protein mutants and those in development in the table below. For more information on these variants or other Coronavirus proteins, please reach out to us. We want to hear from you!

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Spike Ectodomain S1+S2

Spike Ectodomain S1+S2
Protein Coronavirus Type Source Tag Catalog # Bioactivity
Spike Protein (Active Trimer) SARS-CoV-2 HEK293 His 10549-CV Binds ACE-2 (Catalog # 933-ZN)
SARS-CoV-2 CHO His 10586-CV
SARS-CoV HEK293 His 10683-CV
Bat CoV CHO His 10660-CV
Spike Protein (Active Trimer) Biotinylated SARS-CoV-2 HEK293 His, Biotin BT10549 Binds ACE-2 (Catalog # 10544-ZN)
SARS-CoV-2 HEK293 His, Avi-tag AVI10549
  SARS-CoV-2 CHO His, Avi-tag AVI10586
Spike Protein + GCN4-IZ SARS-CoV-2 HEK293 His 10561-CV Binds ACE-2 (Catalog # 933-ZN)
SARS-CoV-2 CHO His 10638-CV
SARS-CoV HEK293 His 10684-CV
SARS-CoV CHO His 10581-CV
Bat CoV HEK293 His 10688-CV Binds ACE-2 (Catalog # 10544-ZN)

Spike RBD

Spike RBD
Protein Coronavirus Type Source Tag Catalog # Bioactivity
Protein Coronavirus Type Source Tag Catalog # Bioactivity
Spike Protein RBD  SARS-CoV-2 HEK293 Fc 10499-CV Binds ACE-2 (Catalog # 933-ZN)
SARS-CoV-2 CHO Fc 10542-CV
SARS-CoV-2 Sf21 Fc 10565-CV
SARS-CoV-2 HEK293 mFc 10657-CV
SARS-CoV-2 HEK293 His 10500-CV
SARS-CoV-2 CHO His 10534-CV
SARS-CoV-2 Tn5 His 10523-CV
SARS-CoV-2 HEK293 Flag 10689-CV
SARS-CoV CHO His 10558-CV
SARS-CoV CHO Fc 10559-CV
SARS-CoV HEK293 His 10583-CV
SARS-CoV HEK293 Fc 10582-CV
MERS-CoV HEK293 His 10636-CV Binds human DPPIV/CD26 (Catalog # 9168-CV)
MERS-CoV CHO His 10621-CV
HCoV-NL63 HEK293 His 10605-CV Binds human ACE-2 (Catalog # 10544-ZN)
HCoV-HKU1 HEK293 His 10600-CV  
HCoV-229E HEK293 His 10612-CV Binds Aminopeptidase N (Catalog # 3815-ZN)
Bat CoV CHO Fc 10556-CV Binds mouse ACE-2 (Catalog # 3437-ZN)
Bat CoV CHO His 10593-CV Binds human ACE-2 (Catalog # 10544-ZN)
Spike Protein RBD (GCN4-IZ trimer) SARS-CoV-2 HEK293 His 10637-CV Binds ACE-2 (Catalog # 933-ZN)
SARS-CoV-2 CHO His 10659-CV
Spike Protein RBD, Biotinylated SARS-CoV-2 HEK293 His BT10500 Binds ACE-2 (Catalog # 10544-ZN)
SARS-CoV-2 HEK293 Avi-tag, Fc AVI10499

S1 Subunit

S1 Domain
Protein Coronavirus Type Source Tag Catalog # Bioactivity
Spike S1 Protein SARS-CoV-2 HEK293 His 10569-CV Binds ACE-2 (Catalog # 933-ZN)
SARS-CoV-2 Sf21 His 10522-CV
SARS-CoV-2 Tn5 Fc 10622-CV
SARS-CoV-2 CHO Fc 10623-CV
SARS-CoV Sf21 His 10570-CV
SARS-CoV HEK293 Fc 10685-CV
MERS-CoV CHO Fc 10606-CV Binds human DPPIV/CD26 (Catalog # 9168-CV)
Bat CoV CHO His 10662-CV Binds ACE-2 (Catalog # 10544-ZN)
Bat CoV HEK293 His, GCN4 10661-CV
Spike S1 Protein biotinylated SARS-CoV-2 HEK293 His BT10569 Binds ACE-2 (Catalog # 10544-ZN)
SARS-CoV-2 CHO His, Avi-tag AVI10693
Spike S1 + HR1/HR2 Fusion SARS-CoV-2 CHO His 10687-CV Binds ACE-2 (Catalog # 933-ZN)

S2 Subunit

Spike RBD
Protein Coronavirus Type Source Tag Catalog # Bioactivity
SARS-CoV-2 Spike S2 Subunit SARS-CoV-2 HEK293 His 10594-CV  
SARS-CoV-2 Tn5 His 10584-CV   
SARS-CoV-2 Spike S2 Subunit (GCN4-IZ) SARS-CoV-2 HEK293 His 10590-CV  
SARS-CoV-2 HEK293 His 10640-CV Resistant to furin (K986P, V987P)

SARS-CoV-2 Spike Protein Variants

Spike RBD
Spike Protein   Description Source Tag Catalog #
Spike RBD Spike 2 N501Y HEK293 His 10730-CV
Spike Protein S2 D614G HEK293 His 10587-CV
D614G CHO His 10620-CV
Spike Protein S2 B.1.1.7 (UK variant)   His Preorder
H69del, V70del, Y144del, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H
Spike Protein S2 H69del, V70del, Y453F, D614G, I692V   His Preorder
Spike Protein S2 D614G, Q677H   His Preorder
Spike Protein S2 B.1.351 (South African variant) D80A, D215G, L242del, A243del, L244del, K417N, E484K, N501Y, D614G, A701V   His Preorder
S1 Subunit S2 D614G HEK293 His 10609-CV
D614G CHO His 10618-CV
S1 Subunit S2 D614G, Q677H   His Preorder
S1 Subunit S2 A222V   His Preorder
Spike RBD Spike 2 V367F HEK293 His 10626-CV
N439K HEK293 His 10714-CV
G476S HEK293 His 10627-CV
S477N HEK293 His 10713-CV
V483A HEK293 His 10628-CV
Spike RBD Spike 2 B.1.351(South Africa Variant) K417N, E484K, N501Y   His Preorder
Spike RBD Spike 2 N439K   His Preorder
Spike RBD Spike 2 Y453F   His Preorder
Spike RBD Spike 2 S477N   His Preorder
Spike RBD Spike 2 E484K   His Preorder

R&D Systems Spike Proteins Beat the Competition!

Our Spike Proteins exhibit higher binding activity to ACE-2 with better purity

SARS-CoV-2 Spike Protein (Active Trimer)

ELISA – Binding Activity

ELISA – Binding Activity

R&D Systems Recombinant SARS-CoV-2 Spike (Active Trimer) (10549-CV) binds Recombinant Human ACE-2 (933-ZN) in a functional ELISA. The binding activity is approximately 4-fold greater than a top competitor’s Spike protein (full ectodomain).

SDS-PAGE

SDS-PAGE

SDS-PAGE of 1 µg of R&D Systems Recombinant SARS-CoV-2 Spike (Active Trimer) (10549-CV) or a competitor’s Spike protein were run under reducing or non-reducing conditions and visualized by silver staining. The R&D Systems Spike protein runs as a single band compared to the competition.

SARS-CoV-2 Spike RBD Protein

ELISA – Binding Activity

SARS-CoV-2 Spike RBD Protein

R&D Systems Recombinant SARS-CoV-2 Spike RBD (10500-CV) binds Recombinant Human ACE-2 (10544-ZN) in a functional ELISA. The binding activity is approximately 3-fold greater than a top competitor’s Spike RBD protein.

SDS-PAGE

SARS-CoV-2 Spike RBD Protein

SDS-PAGE of 1 µg of R&D Systems Recombinant SARS-CoV-2 Spike RBD (10500-CV) or a competitor’s Spike RBD protein were run under reducing or non-reducing conditions and visualized by silver staining. The R&D Systems Spike protein runs as a sharper, more definitive band than the competitor’s Spike RBD protein.

Are all Spike Proteins the Same?

We compared SARS-CoV-2 Spike proteins from two other vendors against R&D Systems SARS-CoV-2 Spike Protein (Active Trimer) (10549-CV) using size exclusion chromatography (SEC). Data shows the three-dimensional size difference between the three Spike proteins. The R&D Systems Spike protein runs at a calculated MW of 367 kDa, consistent with a true trimeric conformation. Both competitor Spike proteins run significantly larger suggesting a higher order oligomeric structure.

R&D Systems SARS-CoV-2 Spike Protein (Active Trimer)

Nucleocapsid and NSP Proteins

Protein   Source Tag Catalog # Bioactivity
SARS-CoV-2 Nucleocapsid Protein S2 Sf21 His 10474-CV Bioactivity not tested, >95% pure by SDS-PAGE
MERS-CoV Nucleocapsid Protein S2 Sf21 His 10521-CV Bioactivity not tested, >95% pure by SDS-PAGE
SARS-CoV-2 NSP8 S2 E. coli His 10633-CV Bioactivity not tested, >90% pure by SDS-PAGE
SARS-CoV-2 NSP9 S2 E. coli His 10631-CV Bioactivity not tested, >95% pure by SDS-PAGE
SARS-CoV-2 NSP10 S2 E. coli His 10630-CV Bioactivity not tested, >95% pure by SDS-PAGE
SARS-CoV-2 NSP16/10 Complex S2 E. coli His 10634-CV Bioactivity not tested, >95% pure by SDS-PAGE

Coronavirus Proteases

Protein Species Source Tag Catalog # Bioactivity
SARS-CoV-2 Papain-like Protease SARS-CoV-2 E. coli GST E-611 Cleaves Ubiquitin-Rhodamine 110 (Catalog # U-555)
SARS Virus Papain-like Protease SARS-CoV E. coli No tag E-610
MERS-CoV Papain-like Protease MERS-CoV E. coli No tag E-609
SARS-CoV-2 3CL Protease SARS-CoV-2 E. coli No tag E-720 Cleaves SARS CoV-2 3CL Protease Substrate, Rh110-conjugated (Catalog # S-720)
SARS-CoV 3CL Protease SARS-CoV E. coli No tag E-718
MERS-CoV 3CL Protease MERS-CoV E. coli No tag E-719

Receptor Recognition

Coronavirus binding to a cell surface receptor is a key mechanism of infection and a major focus of therapeutic research. Using proteins that are bioactive and have the correct conformation is critical for binding and drug development studies. Every protein listed below is QC tested for bioactivity and lot-to-lot consistency.

ACE-2 Receptor Recognition

Protein Species Source Tag Catalog # Bioactivity
ACE-2 Human NS0 His 933-ZN Binds SARS-CoV-2 S Protein RBD (10499-CV)
CHO Fc 10544-ZN
Mouse CHO His 3437-ZN Cleaves the fluorogenic peptide substrate, Mca-YVADAPK(Dnp)-OH (Catalog # ES007)
Rat NS0 His 4516-ZN
Pig HEK293 His 10545-ZN
Dog HEK293 His 10566-ZN
Chicken HEK293 His 10592-ZN
Ferret HEK293 His 10635-ZN
Cyno NS0 His 10619-ZN Binds SARS-CoV-2 S Protein RBD (10499-CV)
Hamster HEK293 His 10578-ZN
Biotinylated ACE-2 Human CHO Avi-tag, His AVI10579 Binds SARS-CoV-2 S Protein RBD (10499-CV)
CHO Avi-tag, Fc AVI10544
HEK293 Avi-tag, His Please Inquire
HEK293 Avi-tag, Fc Please Inquire
NS0 His BT933
CHO Fc BT10544
DPPIV Human NS0 His 9168-SE Cleaves the fluorogenic peptide substrate, Gly-Pro-7-amido-4-methylcoumarin (GP-AMC)
Mouse NS0 His 954-SE
Cyno HEK293 His 9637-SE
Aminopeptidase N/CD13 Human NS0 His 3815-ZN Cleaves the fluorogenic peptide substrate, Ala-7-amido-4-methylcoumarin (Ala-AMC)
Mouse NS0 His 2335-ZN
CEACAM-1 Human NS0 His 2244-CM Inhibits IL-2 secretion by T cells
LY6E Human HEK293 Fc 9970-L6 Inhibits IFN-gamma and IL-2 secretion by T cells
EMMPRIN/CD147 Human NS0 Fc, His 972-EMN Induces active MMP-1 secretion by NHLF human normal lung fibroblasts
Mouse NS0 His 772-EM
Neuropilin-1 Human NS0 His 3870-N1 Binds VEGF 165
Mouse NS0 His 5994-N1
Rat NS0 Fc, His 566-NNS
Rat Sf21 Fc, His 566-N1

Host Cell Proteases

Host cell proteases are involved in coronavirus protein processing and activation. All enzymes listed are bioactive and QC tested to ensure consistency and activity.

Protein Species Source Tag Catalog # Bioactivity
Cathepsin B Human NS0 His 953-CY Cleaves the fluorogenic peptide substrate Z-LR-AMC (Catalog # ES008)
Mouse NS0 His 965-CY
Cathepsin L Human NS0 His 952-CY Cleaves the fluorogenic peptide substrate Z-LR-AMC (Catalog # ES008)
Mouse NS0 His 1515-CY
Furin Human NS0 His 1503-SE Cleaves the fluorogenic peptide substrate pERTKR-AMC (Catalog # ES013)
Mouse CHO His 6450-SE
Elastase/ELA2 Human CHO His 9167-SE Cleaves the fluorogenic peptide substrate, MeOSuc-Ala-Ala-Pro-Val-7-amido-4-methylcoumarin (MeOSuc-AAPV-AMC
Mouse NS0 His 4517-SE

Find More Tools for Coronavirus Research

Antibodies, Assay Kits, Cell Culture, Small Molecules, and more.

See our selection  View SARS-CoV-2 IgG ELISA

Custom Protein Services

Are you looking for something unique? Contact our Custom Protein Team to see how you can leverage over 30 years of protein development experience to meet your needs.

Bulk Proteins

Contact us and see how much you can save by buying in bulk. Supply agreements available.

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Coronavirus Protein FAQs

Find out the answers to some of your frequently asked questions about our coronavirus proteins.

Do you have an active recombinant SARS-CoV-2 Spike protein?

Yes, we offer SARS-CoV-2 active trimer proteins capable of binding to ACE-2. We also have spike subunits spike RBD proteins, and a chimeric spike-Fc fusion protein. Bulk and custom options are also available.

View our spike proteins

 

How may I assess the bioactivity of your proteins?

ELISA or SPR binding assays are currently the best option for bioactivity testing of Spike, S1, RBD, and ACE2. Most researchers will be using these proteins in binding assays, as such we have focused our in-house validation on that application. Low nanomolar binding for most of the Spike, S1, RBD in assays with ACE2 is currently regarded as the gold standard.

What is the difference between the full length ectodomain SARS-CoV-2 Spike (Active Trimer) and SARS-CoV-2 Spike (GCN4-IZ)?

The only difference between the two proteins is presence or lack of the GCN4-IZ domain. The full ectodomain in both proteins is the same sequence (Val16-Lys1211), however both Active Trimer and GCN4-IZ Spike proteins contain the endogenous HR1/HR2 trimerization domains. The SARS-CoV-2 Spike (GCN4-IZ) also includes an ectopic GCN4-IZ (Isoleucine Zipper) trimerization domain in addition to the natural HR1/HR2 trimerization motifs  We made versions of Spike protein both with and without this additional GCN4-IZ motif in case the endogenous HR1/HR2 domains were not sufficient to form trimers when these spike proteins were made as recombinant proteins.

The SARS-CoV-2 Active Trimer products made in CHO and HEK293 cells are true trimers when analyzed by Size Exclusion Chromatography (SEC) analysis, demonstrating that the natural HR1/HR2 motifs are sufficient to form Spike trimers.  Addition of the GCN4-IZ domain results in trimeric species and some slightly more oligomerized species in SEC analysis resulting in a more active trimer protein when used as a ligand with ACE2 proteins in ELISAs. 

Why are there mutations in the full-length spike ectodomain proteins?

In the SARS-CoV-2 Spike Protein, the two mutations K986P and V987P are the corresponding mutations to K968P and V969P in the SARS-CoV Spike Protein, which promote the prefusion conformation (Kirchdoerfer et al. 2018). Two additional mutations in the SARS-CoV-2 Spike Protein R682S and R685S eliminate a furin protease cleavage site, making the Spike Protein resistant to furin cleavage.

Do you have an ACE-2 recombinant protein?

Yes, we have several ACE-2 proteins from different species including human, mouse, rat, hamster, and pig. These have been raised in HEK293, CHO, or NS0 host expression systems. We also have biotinylated versions of human ACE-2.

 

What is the difference in ACE-2 binding affinity of the glycosylated Spike protein and non-glycosylated Spike protein?

Glycosylation of the SAS-CoV-2 Spike RBD protein does not appear to affect its binding affinity to ACE-2. However, it is an important consideration when using these spike proteins as antigen to generate relevant blocking antibodies. In addition, researchers may want to consider glycosylation if using the spike proteins in serological diagnostic assays such as antigen-down ELISAs or lateral flow tests.

Which of the COVID-19 related proteases do you supply?

We have SARS and SARS-CoV-2 virus Papain-like Protease, and the 3CL protease. We also have the related MERS-COV Papain like protease, and its respective 3CL protease.

View Coronavirus Proteases

Read Article: Key Protease Targets for COVID-19

What is the difference between SARS CoV-2 proteins made in different source cells such as HEK293 and CHO?

SARS CoV-2 proteins can be highly glycosylated. When made in eukaryotic cell types such as CHO, HEK293, Sf21, or Tn5, this glycosylation pattern can differ depending on the cell type used. Antibodies made using these proteins might recognize cell type-specific glycan epitopes. In addition, glycans can affect receptor binding interactions, and proteins from a given source cell may work better in your specific assay.

Read Application Note: Glycosylation of the receptor binding domain of COVID-19 virus spike protein.

 

Can your proteins be used in serological assays and release testing assays?

Yes, we have maximized yields to meet the large mass demands required of serological assays and quality control release testing assays. In addition, we have data over multiple lots that demonstrate consistency in our manufacturing process.

If you would like to easily measure human ACE-2 levels by ELISA, our ACE-2 DuoSet® ELISA kit is designed and validated to deliver you the matched antibody pair, protein controls, and detection reagents you need to quantify natural or recombinant ACE-2. A Quantikine ELISA is also in development.

Please contact us for details on specific products and additional data.

Can you synthesize me a COVID-19 related protein conjugated to my fluorophore of choice?

Yes, we are happy to help with custom conjugation requests. We can either start with one of our existing catalog proteins, or custom synthesize a protein and conjugate it to your desired fluorophore.

View Custom Services

Can you synthesize the pro form of IL-1F7b as a treatment for the COVID-19 hyperinflammatory response?

Yes. We can produce custom research-grade proteins suitable for proof-of-concept studies in vitro and in vivo in animal models. We can also produce GMP-compliant proteins for ex vivo use. Our products are not pharmaceutical grade and are not suitable direct injection into human patients.

View Custom Services

Do you have a reliable and accurate serological assay for COVID-19?

Bio-Techne has partnered with Kantaro Biosciences to develop, scale, manufacture, and distribute an antibody test utilizing the Mount Sinai assay as the underlying technology. Kit production capacity is expected to enable laboratories to conduct in excess of 10 million tests.

This IgG antibody test kit is an enzyme-linked immunosorbent assay or ELISA, designed to measure the presence or absence of anti-SARS-CoV-2 antibodies in addition to measuring the titer (level) of antibodies in a sample. It utilizes two virus antigens, the full-length Spike protein, and its Receptor Binding Domain, which is necessary for viral cell entry and is potentially linked with neutralization. The test kit will use a simple patient blood draw and is designed to be easily run by any laboratory in the world without costly proprietary equipment.

About Coronavirus Proteins

COVID-19 research and drug development speed along at an unprecedented pace as the scientific community searches for a cure. At R&D Systems, we understand the importance of quality recombinant proteins and enzymes with documented bioactivity and consistent performance for studying SARS-CoV-2 and other coronaviruses. We offer a range of different Spike RBD, S1 subunit, S2 subunit, and Spike full ectodomain proteins, as well as bioactive Papain-like proteases and 3CL proteases. With over 95% purity, the SARS-CoV-2 Nucleocapsid protein is an ideal antigen. Trusted for over 35 years, R&D Systems is the leading provider of recombinant proteins to the life science community.

Spike Protein

The Coronavirus Spike protein (S Protein) is one of four major structural proteins covering the surface of each virion. The Spike protein is a highly glycosylated, type I transmembrane protein responsible for host cell entry. Structurally, there are two domains, S1 and S2, that play major roles in receptor binding and membrane fusion. Within the N-terminal S1 domain is the receptor binding domain (Spike RBD protein). The Spike RBD binds to the host cell and initiates viral infection. The SARS-CoV-2 Spike RBD tightly associates with human ACE-2. Once the Spike S1 domain binds to its host receptor, conformational changes occur in the Spike S2 domain allowing for membrane attachment and eventually transfer of the nucleocapsid into the cell. Because of its essential role during Coronavirus infection, the Spike protein is major therapeutic target.

Nucleocapsid Protein

The Coronavirus Nucleocapsid protein (N Protein) is a multifunctional RNA-binding protein required for viral RNA transcription, replication, and packaging. The Nucleocapsid protein consists of three domains, an N-terminal RNA-binding domain, a central intrinsically disordered region, followed by a C-terminal dimerization domain. The RNA-binding domain contains multiple positively charged binding surfaces that form charged interactions with RNA promoting its helical arrangement. The Nucleocapsid protein is highly antigenic making it an attractive target for vaccine development and serological assays.

Papain-like Protease

The Coronavirus Papain-like protease (PLPro) is one of several nonstructural proteins (nsps) and along with 3CL Protease, is responsible for processing of viral proteins into functional, mature subunits during maturation. For example, PLPro cleaves a site at the amino-terminal end of the viral replicase region. In addition to its role in viral protein maturation, Papain-like protease exhibits both a deubiquitinating and deISG15ylating activity. In vivo, this protease antagonizes innate immunity by acting on IFN beta and NF- kappa B signaling pathways. Purified PLPro is used in vitro with polyubiquitin substrates demonstrating a strong preference for K48 linkages.

3CL Protease

The Coronavirus 3CL protease (3CLpro) is the other main protease in addition to the Papain-like protease and is required for processing of viral polypeptides into distinct, functional proteins. The SARS-CoV-2 3CL Protease is a C30-type cysteine protease located within the non-structural proteins 3 (NS3) region of the viral polypeptide. Analysis of the Coronavirus genome reveals at least 11 sites of cleavage for the 3CL Protease, many containing the amino acid sequence LQ[S/A/G]. In addition to the Papain-Like Protease, 3CLpro presents a promising therapeutic target for COVID-19. One attractive advantage of 3CLpro is that no human proteases are known to have a similar cleavage specificity making inhibitors of 3CLpro unlikely to cause mechanism-based toxicity.