Reagent Bank for SARS-CoV-2 Research

The recent COVID-19 pandemic caused by SARS-CoV-2 has influenced both the health care systems and economies around the world, and has posed challenges to vaccines, drugs and diagnostics development. Since the outbreak, Sino Biological have been actively tracking the change and movement of the virus to make products “up to date". Our SARS-CoV-2-related recombinant protein and antibody products have been widely used by researchers across different disciplines and have since generated near 500 citations so far. In addition, those reagents in COVID-19 have been accelerating the progress in serological assay development against SARS-CoV-2. We have also developed the largest bank of recombinant mutant proteins of spike protein, its segments (e.g., S1, RBD, S2), and nucleocapsid. The variant proteins have been actively used by scientists to assess the phenomena of “antibody evasion”caused by the mutagenesis of key residues in the spike protein.

Recombinant SARS-CoV-2 Antigens

Recombinant Spike

Featured SARS-CoV-2 Spike Proteins

Cat# Antigen Expressed Host Tag
40591-V08H S1 HEK293 Cells His
40590-V08B S2 Baculovirus-Insect Cells His
40592-V05H RBD HEK293 Cells mFc
40592-V08B RBD Baculovirus-Insect Cells His
40592-V08H RBD HEK293 Cells His

More SARS-CoV-2 Spike Proteins

Cat# Antigen Expressed Host Tag
40589-V08H4 S1+S2 ECD HEK293 Cells His
40591-V02H S1 HEK293 Cells Fc
40591-V05H1 S1 HEK293 Cells mFc
40591-V08B1 S1 Baculovirus-Insect Cells His
40591-V08H-B Biotinylated S1 HEK293 Cells His
40591-V27H-B Biotinylated S1 HEK293 Cells AVI & His
40591-V41H S1 NTD HEK293 Cells Fc & AVI
40591-V41H-B Biotinylated S1 NTD HEK293 Cells Fc & AVI
40591-V49H S1 NTD HEK293 Cells His & AVI
40591-V49H-B Biotinylated S1 NTD HEK293 Cells His & AVI
40589-V08B1 S1+S2 ECD Baculovirus-Insect Cells His
40589-V08B1-B Biotinylated S1+S2 ECD Baculovirus-Insect Cells His
40589-V27B-B Biotinylated S1+S2 ECD Baculovirus-Insect Cells AVI & His
40590-V02H S2 HEK293 Cells Fc
40590-V05B S2 Baculovirus-Insect Cells mFc
40590-V08B-B Biotinylated S2 Baculovirus-Insect Cells His
40590-V08H1 S2 HEK293 Cells His
40592-V02H RBD HEK293 Cells Fc
40592-V08B-B Biotinylated RBD Baculovirus-Insect Cells His
40592-V08H-B Biotinylated RBD HEK293 Cells His
40592-V27B-B Biotinylated RBD Baculovirus-Insect Cells AVI & His
40592-V27H-B Biotinylated RBD HEK293 Cells AVI & His
40592-V31H RBD HEK293 Cells rFc
40592-VNAH RBD HEK293 Cells  

Recombinant Nucleocapsid

Featured SARS-CoV-2 Nucleocapsid Proteins

Cat# Antigen Expressed Host Tag
40588-V08B Nucleocapsid Baculovirus-Insect Cells His
40588-V07E Nucleocapsid E. coli His
HPLC-40588-V07E Nucleocapsid E. coli His

More SARS-CoV-2 Nucleocapsid Proteins

Cat# Antigen Expressed Host Tag
40588-V07E-B Nucleocapsid E. coli His
40588-V07E10 Nucleocapsid NTD E. coli His
40588-V07E5 Nucleocapsid CTD E. coli His
40588-V07E6 Nucleocapsid E. coli His
40588-V08B-B Nucleocapsid Baculovirus-Insect Cells His
40588-V27B-B Nucleocapsid Baculovirus-Insect Cells AVI & His

Recombinant Variant Bank

Featured SARS-CoV-2 Variants

Lineage Mutations Cat# Antigen Tag
B.1.1.7 N501Y 40592-V02H1 RBD Fc
B.1.1.7 N501Y 40592-V08H82 RBD His
B.1.1.7 N501Y 40592-V31H1 RBD rFc
B.1.351 K417N, E484K, N501Y 40592-V08H85 RBD His
B.1.351 E484K 40592-V31H2 RBD rFc
B.1.351 K417N, E484K, N501Y 40592-V31H4 RBD rFc
B.1.351 K417N 40592-V31H6 RBD rFc
B.1.617 L452R, E484Q 40592-V08H88 RBD His
B.1.617 L452R 40592-V08H28 RBD His
B.1.617 E484Q 40592-V08H81 RBD His
P.1 K417T, E484K, N501Y 40592-V08H86 RBD His
P.1 K417T, E484K, N501Y 40592-V31H5 RBD rFc
P.1 K417T 40592-V31H7 RBD rFc
B.1.1.7 HV69-70 deletion, Y144 deletion, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H 40589-V08B6 S1+S2 ECD His
B.1.351 L18F, D80A, D215G, LAL242-244 deletion, R246I, K417N, E484K, N501Y, D614G, A701V 40589-V08B7 S1+S2 ECD His
B.1.351 D80A, K417N, E484K, N501Y, D614G, A701V 40589-V08B9 S1+S2 ECD His
P.1 L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, V1176F 40589-V08B10 S1+S2 ECD His
P.1 L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I 40589-V08B8 S1+S2 ECD His

Enzymes, NSPs, and More

Cat# Antigen Expressed Host Tag
40593-V07E PLpro E.coli His
40594-V07B 3CLpro Baculovirus-Insect Cells His
40594-V56B 3CLpro Baculovirus-Insect Cells His & AVI
40594-V56E 3CLpro E. coli His & AVI
40595-V08B RDRP Baculovirus-Insect Cells His
40596-V07E Helicase E. coli His
40598-V07E Methyltransferase E. coli His
40609-V10E3 Envelope E. coli His & MBP
40599-V07E NSP10 E. coli His
40599-VNCE NSP10 E. coli
40619-V40E NSP9 E. coli His & AVI
40618-V17E NSP8 E. coli AVI
40617-VNCE NSP7 E. coli
40638-V07E NSP3 Baculovirus-Insect Cells His

SARS-CoV-2 Receptor ACE2

Cat# Species Expressed Host Tag Activity
10108-H02H Human HEK293 Cells Fc Bind to Spike (40591-V08B1)
10108-H05H Human HEK293 Cells mFc Enzyme Activity
10108-H08B HPLC-verified Human Baculovirus-Insect Cells His Bind to Spike (40592-V05H)
10108-H08H HPLC-verified Human HEK293 Cells His Bind to Spike (40592-V05H) Enzyme Activity
10108-H08H-B Biotinylated Human HEK293 Cells His Bind to Spike (40592-V05H)
10108-H27B-B Human Baculovirus-Insect Cells AVI & His Bind to Spike (40592-V05H)
50249-M03H Mouse HEK293 Cells His & Fc
50249-M08H Mouse HEK293 Cells His
51031-M08H Mouse HEK293 Cells His Enzyme Activity
80031-R08H Rat HEK293 Cells His Enzyme Activity
90211-C02H Rhesus HEK293 Cells Fc Enzyme Activity
90211-C08H Rhesus HEK293 Cells His Enzyme Activity

Anti SARS-CoV-2 Antibodies

Sino Biological has developed a large collection of SARS-CoV-2 antibodies for research. Technical information about specificity and sensitivity, cross-reactivity, neutralizing potential, and their validated applications are illustrated here.

High Affinity
Binding affinity has been validated by BLI assay.

  • BLI: KD=0.006 nM

    Anti-Spike Rabbit MAb (cat#:40592-R001)

  • BLI: KD=0.01 nM

    Anti-N Rabbit MAb (cat#:40143-R040)

  • High Specificity
    ELISA assay has been taken to validate the cross-reactivity with Spike antigens from different Human Coronaviruses.

    No cross-reactivity with SARS-CoV, MERS-CoV, HKU1, 229E, NL63, and OC43.

  • Neutralization Assay
    The anti-RBD neutralizing antibody could effectively block the binding between recombinant spike RBD and ACE2 protein, and inhibit the infection of spike pseudovirus to ACE2 overexpressed HEK293T cells.

    Anti-Spike RBD Mouse MAb (cat#: 40592-MM57)

The S and N detection kits employ a standard sandwich ELISA, allowing rapid quantification of the N and S antigens.
• All antibodies used in the kits are in-house developed monoclonal antibodies, ensuring batch-to-batch consistency.
• These assays may be used to quantify antigens on the surface of SARS-CoV-2 and/or pseudovirus, as well as antigens expressed recombinantly.

SARS-CoV-2 N Detection Kit
(KIT40588)
More about SARS-CoV-2 Antigen Detection Assay
• Inhibitor Screening Kit
• Antibody Titer Assay Kits

Sino Biological announced this week that the company has launched the world first coronavirus antigen array under its new brand SinommuneTM. This product is co-developed by Nanommune Inc., a UCI-based biotech company specializing in array technology. This antigen array is specifically designed for high throughput sero-surveillance studies of COVID-19 Coronavirus, and other virus that can lead to upper respiratory infections. The SinommuneTM is constructed by printing recombinant antigens on a nitrocellulose-coated membrane. It can analyze serum antibodies against 66 antigens from 23 types of viruses known to cause respiratory tract infections, including SARS-CoV-2 and the other six coronaviruses.

HCoV-OC43 HCoV-229E SARS-CoV
HCoV-NL63 HCoV-HKU1 MERS-CoV
SARS-CoV-2 Influeza virus RSV
Metapneumovirus Parainfluenza Adenovirus

SARS-CoV-2 Reagents and Services Related Citations

Up to 30th April, there are near 500 publised papers and 120 pre-publised publications that have cited SARS-CoV-2 reagents or services providing by Sino Biological Inc.

Title Journal Author Year
Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity Cell Thomson, E,et al. 2021
Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection Cell Brouwer, PJM,et al. 2021
The antigenic anatomy of SARS-CoV-2 receptor binding domain Cell Dejnirattisai, W,et al. 2021
BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection Cell Mills, R,et al. 2021
COVID-19 immune features revealed by a large-scale single cell transcriptome atlas Cell Ren, X,et al. 2021
Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia Cell Asarnow, D,et al. 2021
Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients\' B cells Cell Cao, Y,et al. 2020
Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies Cell Wrapp, Daniel,et al. 2020
Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment Cell Sun, J,et al. 2020
Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2 Cell Wang, H,et al. 2020
A universal design of betacoronavirus vaccines against COVID-19, MERS and SARS Cell Dai, L,et al. 2020
The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Cell Li, Q,et al. 2020
A thermostable mRNA vaccine against COVID-19 Cell Zhang, N,et al. 2020
High potency of a bivalent human VH domain in SARS-CoV-2 animal models Cell Li, W,et al. 2020
Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology Cell Piccoli, L,et al. 2020
Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant Cell Yurkovetskiy, L,et al. 2020
Structurally Resolved SARS-CoV-2 Antibody Shows High Efficacy in Severely Infected Hamsters and Provides a Potent Cocktail Pairing Strategy Cell Du, S,et al. 2020
Imbalance of regulatory and cytotoxic SARS-CoV-2-reactive CD4+ T cells in COVID-19 Cell Meckiff, B,et al. 2020
Quick COVID-19 Healers Sustain Anti-SARS-CoV-2 Antibody Production Cell Chen, Y,et al. 2020
Compromised humoral functional evolution tracks with SARS-CoV-2 mortality Cell Zohar, T,et al. 2020
A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2 Cell Hassan, AO,et al. 2020
Compromised SARS-CoV-2-specific placental antibody transfer Cell Atyeo, C,et al. 2020
Title Journal Author Year
Potent human neutralizing antibodies elicited by SARS-CoV-2 infection Nature Bin Ju,et al. 2020
The Pathogenicity of SARS-CoV-2 in hACE2 Transgenic Mice Nature Linlin Bao et al. 2020
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody Nature Dora Pinto,et al. 2020
Proteomics of SARS-CoV-2-infected host cells reveals therapy targets Nature Bojkova, D,et al. 2020
Potent neutralizing antibodies directed to multiple epitopes on SARS-CoV-2 spike Nature Liu, L,et al. 2020
Structures and distributions of SARS-CoV-2 spike proteins on intact virions Nature Ke, Z,et al. 2020
COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice Nature Zheng, J,et al. 2020
A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate Nature Sanchez-Felipe, L,et al. 2020
Title Journal Author Year
Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection Science Dan, JM,et al. 2021
Reinfection could not occur in SARS-CoV-2 infected rhesus macaques Science Linlin Bao,et al. 2020
Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2 Science Renhong Yan et al. 2020
SARS-CoV-2 productively infects human gut enterocytes Science Lamers, MM,et al. 2020
Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model Science Rockx, B,et al. 2020
DNA vaccine protection against SARS-CoV-2 in rhesus macaques Science Yu, J,et al. 2020
A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2 Science Xiangyang Chi,et al. 2020
Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent theraprutic antibody Science Zhe Lv,et al. 2020
De novo design of picomolar SARS-CoV-2 miniprotein inhibitors Science Cao, L,et al. 2020
Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2 Science Chan, KK,et al. 2020
Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy Science Gu, H,et al. 2020
Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques Science Deng, W,et al. 2020
Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability Science Brouwer, PJM,et al. 2020
Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail Science Hansen, J,et al. 2020
SARS-CoV-2 infection protects against rechallenge in rhesus macaques Science Chandrashekar, A,et al. 2020

SARS-CoV-2 (2019-nCoV, Novel Coronavirus 2019) has led to pneumonia (COVID-19) that sickened over 56.9M people worldwide. Same as all other coronaviruses, the genome of SARS-CoV-2 (2019-nCoV) encodes the spike protein, the envelope protein, the membrane protein, and the nucleocapsid protein.

The spike protein (S-protein) is the common target for neutralizing antibodies and vaccines. Spike protein contains two subunits, S1 and S2. S1 contains a receptor binding domain (RBD), which is responsible for recognizing and binding with the cell surface receptor. S2 subunit contains other basic elements needed for the membrane fusion. SARS-CoV-2 (2019-nCoV) (ref.) can infect the human respiratory epithelial cells through interaction with huamn ACE2. Indeed, the recombinant Spike protein can bind with recombinant ACE2 protein.

The Nucleocapsid Protein (N-protein) is the most abundant protein in coronavirus. The N-protein is a highly immunogenic phosphoprotein, and it is normally very conserved. The N protein of coronavirus is often used as a marker in diagnostic assays.

Sino Biological is the first company in the world to produce recombinant proteins of SARS-CoV-2. We launched the spike protein on Jan 22nd, only 12 days after the sequence is published. Till this day, Sino Biological has developed a large panel of reagents for COVID19 research. The available products include hundreds of antigens (the N protein, S protein, the S1 and S2 subunits of the S protein, and the RBD domain of the S proteins, Plpro, MTase, NSP3, NSP8,NSP9), monoclonal antibodies, ELISA kits, and expression vectors for SARS-CoV-2 and its receptor. These reagents have supported hundreds of research groups around the globe for their vaccine and antibody development works. Sino Biological is also offering pseudovirus-based infection assay services, allowing rapid screening of antibodies and compounds for neutralization potential.

 

Reference

• Xintian Xu.Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission.SCIENCE CHINA Life Sciences.2020
• Bo Diao, Zeqing Feng.Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.medRxiv preprint

 

Capacity of Viral Reagents Development

• 2009.5 Launched Recombinant Influenza A H5N1 Hemagglutinin Protein

• 2009.12 Launched Influenza A H5N1 HA ELISA Pair Set and H1N1 HA ELISA Pair Set

• 2012.12 Launched MERS-CoV Spike Protein(S1,S2,S-RBD),NP protein within 50 Days after Sequence Published.

• 2013.4 Completed R&D of H7N9 HA Protein & H7N9 NA Protein in 12 Days.

• 2013.10 Launched SARS CoV Spike Protein, NP Protein.

• 2014.2 Completed R&D of EBOV NP, GP, VP40, VP24 Proteins.

• 2016.6 Completed R&D of ZIKV Envelope, Membrane protein in 14 Days.

• 2020.1 Completed R&D of SARS-CoV-2 (2019-nCoV) Viral Proteins (Spike, S1, S2, RBD protein) in 12 Days.

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