Genetex COVID-19

Research Solutions for Coronavirus – Genetex

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously known as 2019 Novel Coronavirus (2019-nCoV), is a positive-sense, single-stranded RNA virus that causes the potentially lethal COVID-19 respiratory tract infection. This new virus belongs to the genus Betacoronavirus, which also includes SARS-CoV and MERS-CoV. The first case of COVID-19 was detected in December, 2019 in Wuhan, China, and has now been declared a pandemic (1). Human-to-human spread has been confirmed, with a suspected incubation period of ~2-14 days. There are some reports of transmission in the absence of clear symptoms, though infected people are likely most contagious due to coughing and sneezing that expel respiratory droplets.

With SARS-CoV-2 now reaching pandemic status, researchers and clinicians have been working furiously to learn more about the virus’s biology and pathogenesis as well as how to treat the more clinically aggressive COVID-19 cases. As with any viral pathogen, understanding how SARS-CoV-2 enters host cells is of great significance.

In their study published very recently in Cell, Hoffmann et al. confirm findings reported by Zhou et al. that angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV-2, as it is for SARS-CoV (2, 3). In addition, they identify the serine protease TMPRSS2 as a critical factor in the priming of the SARS-CoV-2 spike (S) protein, an essential step for viral entry into host cells through fusion of the viral and cellular membranes. The authors also demonstrate that the serine protease inhibitor camostat mesylate, an agent that has already seen clinical application as a treatment for chronic pancreatitis in Japan, is able to interfere with SARS-CoV-2 infection of lung cells. Finally, the study presents data that antibodies generated to SARS-CoV S protein may have some protective activity against SARS-CoV-2. Together, this work expands our knowledge of key factors involved in SARS-CoV-2’s entry into cells and reveals some promising avenues for SARS-CoV-2-directed therapies.

To further expedite the identification of agents with activity against SARS-CoV-2, the WHO’s SOLIDARITY study will assess the potential utility of four different classes of clinically known drugs or drug combinations against the virus (4). The four arms include the viral polymerase inhibitor remdesivir, the anti-malarial agents chloroquine and hydroxychloroquine, the HIV protease inhibitors lopinavir and ritonavir, and lopinavir/ritonavir with interferon-beta. This study, which is one of many ongoing trials that are reviewing more than a dozen possible therapies, is stripped down to accelerate data acquisition and be accessible to physicians everywhere. The central focus of many of these trials is to evaluate existing agents with acceptable safety profiles (e.g., the serine protease inhibitor camostat mesylate) that are amenable to repurposing for use against SARS-CoV-2. In addition, compounds previously found to have activity against SARS-CoV, MERS-CoV, or other viruses are being reexamined, as is the use of convalescent plasma from recovered COVID-19 patients and monoclonal antibodies targeting viral components (5). The singular determination to fight this virus as a world community is now widely appreciated as the only path to eventual success.

GeneTex is proud to offer an extensive line of research antibodies and proteins to support the study of SARS-CoV-2, several of which were validated using virus-infected cell lysates. Please see the highlighted products below or click the button to see more product information.

Antibodies

SARS-CoV / SARS-CoV-2 (COVID-19) spike antibody [1A9]

(GTX632604)

SARS-CoV / SARS-CoV-2 (COVID-19) nucleocapsid antibody [6H3]

(GTX632269)

ACE2 antibody [N1N2], N-term

(GTX101395)

SARS-CoV-2 (COVID-19) spike antibody

(GTX135356)

SARS-CoV-2 (COVID-19) nucleocapsid antibody

(GTX135357)

SARS-CoV / SARS-CoV-2 (COVID-19) ORF7a antibody [3C9]

(GTX632602)

SARS-CoV / SARS-CoV-2 (COVID-19) NSP8 antibody [5A10]

(GTX632696)

TMPRSS2 antibody [N2C3]

(GTX100743)

Additional Antibodies

Product Name Code
ACE2 antibody GTX15349
ACE2 antibody [SN0754] Rabbit Monoclonal GTX01160
SARS-CoV / SARS-CoV-2 (COVID-19) spike antibody [CR3022] GTX01555
SARS-CoV-2 (COVID-19) nucleocapsid antibody [HL146] GTX635680
SARS-CoV-2 (COVID-19) nucleocapsid antibody [HL249] GTX635678
SARS-CoV-2 (COVID-19) nucleocapsid antibody [HL344] GTX635679
SARS-CoV-2 (COVID-19) Spike S1 antibody [HL1] GTX635656
SARS-CoV-2 (COVID-19) Spike S1 antibody [HL134] GTX635671
SARS-CoV-2 (COVID-19) Spike S1 antibody [HL263] GTX635672
SARS-CoV-2 (COVID-19) Spike S1 antibody [HL6] GTX635654
SARS-CoV-2 (COVID-19) Spike antibody GTX135384
SARS-CoV-2 (COVID-19) Spike antibody GTX135385
SARS-CoV-2 (COVID-19) Spike antibody GTX135386
SARS-CoV-2 (COVID-19) spike antibody GTX135360
SARS-CoV-2 (COVID-19) nucleocapsid antibody GTX135361

Proteins

SARS-CoV-2 (COVID-19) nucleocapsid protein

(GTX135357-pro)

Human ACE2 protein (active)

(GTX01179-pro)

SARS-CoV-2 (COVID-19) Spike S1 protein, His and Avi tag (active)

(GTX01548-pro)

SARS-CoV-2 (COVID-19) Spike RBD protein, His tag (active)

(GTX01546-pro)

Additional Proteins

Product Name Code
Human ACE2 protein, His and Avi tag GTX01550-pro
SARS-CoV-2 (COVID-19) Envelope protein, His and Avi tag GTX01547-pro
SARS-CoV-2 (COVID-19) Spike S1 protein, His tag (active) GTX01554-pro
SARS-CoV-2 (COVID-19) nucleocapsid protein GTX135592-pro

Inhibitors

Camostat mesylate

(GTX01523)

SARS-CoV-2 proteins FFPE cell blocks

Product Name Code
SARS-CoV-2 (COVID-19) Spike FFPE Cell Pellet Block HEK 293 GTX435640
SARS-CoV-2 (COVID-19) Spike S1 FFPE Cell Pellet Block HEK 293 GTX435643
SARS-CoV-2 (COVID-19) Spike S2 FFPE Cell Pellet Block HEK 293 GTX435644
SARS-CoV-2 (COVID-19) Nucleocapsid FFPE Cell Pellet Block HEK 293 GTX435641
SARS-CoV-2 (COVID-19) Envelope FFPE Cell Pellet Block HEK 293 GTX435642
SARS-CoV-2 (COVID-19) Membrane FFPE Cell Pellet Block HEK 293 GTX435645

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously known as 2019 Novel Coronavirus (2019-nCoV), is a positive-sense, single-stranded RNA virus that causes the potentially lethal COVID-19 respiratory tract infection.
This new virus belongs to the genus Betacoronavirus, which also includes SARS-CoV and MERS-CoV.

SARS-CoV-2 morphology

Components of the viral envelope:

1.Spike (S) protein:

  • A large transmembrane protein that project from the virion surface (140 kDa). Forms a trimeric protein.
  • Has multiple potential glycosylation sites, highly glycosylated. (180 kDa)
  • Can be cleaved to 2 subunits, the amino-terminal S1 and the carboxy-terminal S2. The S1 domain is the most divergent region of the molecule, and S2 is more conserved.
  • The receptor-binding domains (RBDs) are shown in S1, which mediates viral entry.

2.Membrane (M) protein:

  • The most abundant constituent of coronaviruses.
  • M proteins within each coronavirus group are moderately well conserved.

3.Envelope (E) protein:

  • A small polypeptide of around 10 kDa.
  • A minor component of virion.

Structural protein inside the virion:

1.Nucleocapsid (N) protein:

  • Wraps RNA genome and forms a threadlike helical structure.
  • Phosphorylation may related to virion assembly.
  • Molecular weight: 46 kDa

SARS-CoV-2 viral entry

  • Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV-2, as it is for SARS-CoV.
  • TMPRSS2, a serine protease, is a critical factor in the priming of the SARS-CoV-2 spike protein. This is an essential step for viral entry into host cells through fusion of the viral and cellular membranes.
  • A serine protease inhibitor camostat mesylate is able to interfere with SARS-CoV-2 infection of lung cells.

The SARS-CoV-2 has a ~29.9 kilobase positive-sense RNA genome that contains as many as 29 open reading frames. Though the exact number of functional proteins remains to be established, there are at least 16 nonstructural proteins (nsp), four structural proteins, and at least six or seven accessory proteins. Based on previous work with SARS-CoV and other coronaviruses, scientists have identified functions for the majority of these factors, though work is ongoing. A schematic of the SARS-CoV-2 genome is shown in the figure above, while the known or hypothesized functions of the viral proteins, based on studies of SARS-CoV and other coronaviruses, are summarized below in Table 1.

GeneTex is proud to offer an extensive line of reagents to support the study of SARS-CoV-2/COVID-19. Please see Table 2 and Table 3 below to view listings of GeneTex’s antibodies and recombinant proteins available now to accelerate your SARS-CoV-2/COVID-19 research.

Table 1. Putative Functions of SARS-CoV-2 Proteins

ProteinFunctionsReferences
Spike (S)Spike full-length (~1273 a.a. in SARS-CoV-2) protein precursor is cleaved into glycosylated subunits, S1 and S2 (S2’). S1 binds to the host’s receptor, ACE2, while S2 mediates viral and host membrane fusion.1
Nucleocapsid (N)Nucleocapsid (~419 a.a. in SARS-CoV-2) binds viral genomic RNA and forms a helical ribonucleocapsid. Involved in genome protection, viral RNA replication, virion assembly, and immune evasion. Interacts with M and nsp3 proteins.2
Membrane (M)Membrane/matrix protein (~222 a.a. in SARS-CoV-2) is the most abundant structural component of the virion, and very conserved. Mediates assembly and budding of viral particles through recruitment of other structural proteins to “ER-Golgi-intermediate compartment (ERGIC)”. Interaction with N for RNA packaging into virion. Interacts with accessory proteins 3a and 7a. Mitigation of immune response?3
Envelope (E)Envelope small membrane protein (~75 a.a. in SARS-CoV-2) is a single-pass type III membrane protein involved in viral assembly, budding, and pathogenesis. Localizes to ERGIC. Forms a homopentameric ion channel and is a viroporin. Interacts with M, N, 3a, and 7a.4
nsp1Nonstructural protein 1 (nsp1; ~180 a.a. in SARS-CoV-2) likely inhibits host translation by interacting with 40S ribosomal subunit, leading to host mRNA degradation through cleavage near their 5’UTRs. Promotes viral gene expression and immunoevasion in part by interfering with interferon-mediated signaling.5
nsp2nsp2 (~638 a.a. in SARS-CoV-2) interacts with host factors prohibitin 1 and prohibitin 2, which are involved in many cellular processes including mitochondrial biogenesis. It appears that nsp2 may change the intracellular milieu and perturb host intracellular signaling.6
nsp3nsp3 (~1945 a.a. in SARS-CoV-2) is a papain-like protease (PLpro) and multi-pass membrane protein that processes the viral polyprotein to release nsp1, nsp2, and nsp3. It also exhibits deubiquitinating and deISGylating activities. Interacts with nsp4 and nsp6.7
nsp4nsp4 (~500 a.a. in SARS-CoV-2) is required for viral replication by inducing (with nsp3) assembly of, and localizing to, double-membrane cytoplasmic vesicles. Multi-pass membrane protein.8
nsp5nsp5 (3CLpro; ~306 a.a. in SARS-CoV-2) cleaves at 11 sites in the polyprotein to release nsp4-nsp16. It is also responsible for nsp maturation.9
nsp6nsp6 (~290 a.a. in SARS-CoV-2) is a multi-pass membrane protein that induces double-membrane vesicles in infected cells with nsp 3 and nsp4. It also limits autophagosome expansion and interferes with autophagosome delivery of viral factors to lysosomes for destruction.10,11
nsp7nsp7 (~83 a.a. in SARS-CoV-2) forms a hexadecamer with nsp8 as a cofactor for the RNA-dependent RNA polymerase nsp12. May have processivity or RNA primase function.12
nsp8nsp8 (~198 a.a. in SARS-CoV-2) forms a hexadecamer with nsp7 as a cofactor for the RNA-dependent RNA polymerase nsp12. May have processivity or RNA primase function. Mutation of certain residues in nsp8 is lethal to SARS-CoV by impacting RNA synthesis.13
nsp9nsp9 (~113 a.a. in SARS-CoV-2) functions in viral replication as a dimeric ssRNA-binding protein.13
nsp10nsp10 (~139 a.a. in SARS-CoV-2) forms a dodecamer and interacts with both nsp14 and nsp16 to stimulate their respective 3’-5’ exoribonuclease and 2’-O-methyltransferase activities in the formation of the viral mRNA capping machinery.13
nsp11nsp11 (~13-23 a.a., depending on the CoV species) is a pp1a cleavage product at the nsp10/11 boundary. For pp1ab, it is a frameshift product that becomes the N-terminal of nsp12. Its function, if any, is unknown.13
nsp12nsp12 (~932 a.a. in SARS-CoV-2) is the RNA-dependent RNA polymerase (RdRp) performing both replication and transcription of the viral genome. It has >95% identity to the SARS-CoV polymerase and is inhibited by the nucleoside analogue Remdesivir.13
nsp13nsp13 (~601 a.a. in SARS-CoV-2) is a multifunctional superfamily 1 helicase capable of using both dsDNA and dsRNA as substrates with 5’-3’ polarity. In addition to working with nsp12 in viral genome replication, it is also involved in viral mRNA capping. It associates with nucleoprotein in membranous complexes.14
nsp14nsp14 (~527 a.a. in SARS-CoV-2) has both 3’-5’ exoribonuclease (proofreading during RNA replication) and N7-guanine methyltransferase (viral mRNA capping) activities. Interacts with nsp10.13
nsp15nsp15 (~346 a.a. in SARS-CoV-2) is an endoribonuclease that favors cleavage of RNA at the 3’-ends of uridylates. Loss of nsp15 affects both viral replication and pathogenesis. It is also required for evasion of host cell dsRNA sensors.15
nsp16nsp16 (~298 a.a. in SARS-CoV-2) interacts with and is activated by nsp10. Its 2’-O-methyltransferase activity is essential for viral mRNA capping. It may also work against host cell antiviral sensors.13
ORF3aORF3a (~275 a.a. in SARS-CoV-2) is a multi-pass membrane protein that forms a homotetrameric viroporin in SARS-CoV. It interacts with accessory protein 7a, M, S and E. May be involved in viral release. Importantly, it also activates both NF-kB and NLRP3 inflammasome and contributes to the generation of cytokine storm.16
ORF6ORF6 (~61 a.a. in SARS-CoV-2) appears to be a virulence factor in SARS-CoV. It was shown to be an antagonist of type I interferons (IFNs) and is involved in viral escape from the host innate immune system.17
ORF7aORF7a (~121 a.a. in SARS-CoV-2) is a type I membrane protein that interacts with bone marrow stromal antigen 2 (BST-2) in SARS-CoV. BST-2 tethers virions to the host’s plasma membrane. ORF7a binding inhibits BST-2 glycosylation and interferes with this restriction activity. ORF7a also interacts with S, M, E, and ORF3a in SARS-CoV.18
ORF7bORF7b (~43 a.a. in SARS-CoV-2) is a type III integral transmembrane protein in the Golgi apparatus. In SARS-CoV, it appears to be a viral attenuation factor.19
ORF8ORF8 (~121 a.a. in SARS-CoV-2) has only 30% identity to the intact ORF8 of SARS-CoV and might be a luminal ER membrane-associated protein. It may trigger ATF6 activation and affect the unfolded protein response (UPR).20,21,22
ORF9bORF9b (~97 a.a. in SARS-CoV-2) is coded for in an alternative ORF within the N gene. No function is known, though the SARS-CoV protein interacts with nsp5, nsp14, and ORF6. There is limited evidence it may bind to lipids.23
ORF10ORF10 (~38 a.a. in SARS-CoV-2) has no known function but might have a regulatory role involving interaction with another factor(s).24
ProteinFunctionsReferences

Table 2. Antibodies for SARS-CoV-2/COVID-19 Research

Cat. No. Product Name Clonality Applicatoins
GTX632604 SARS-CoV / SARS-CoV-2 (COVID-19) spike antibody [1A9] Ms mAb WB, ICC/IF, FACS
GTX632269 SARS-CoV / SARS-CoV-2 (COVID-19) nucleocapsid antibody [6H3] Ms mAb WB, ICC/IF, ELISA, sELISA
GTX632696 SARS-CoV / SARS-CoV-2 (COVID-19) NSP8 antibody [5A10] Ms mAb WB
GTX632602 SARS-CoV / SARS-CoV-2 (COVID-19) ORF7a antibody [3C9] Ms mAb WB, ICC/IF
GTX135356 SARS-CoV-2 (COVID-19) spike antibody Rb pAb WB, ICC/IF, ELISA
GTX135360 SARS-CoV-2 (COVID-19) spike antibody Rb pAb WB, ICC/IF, ELISA
GTX135357 SARS-CoV-2 (COVID-19) nucleocapsid antibody Rb pAb WB, ICC/IF, ELISA
GTX135361 SARS-CoV-2 (COVID-19) nucleocapsid antibody Rb pAb WB, ICC/IF, ELISA, sELISA
GTX101395 ACE2 antibody [N1N2], N-term Rb pAb WB, IHC-P, FACS
GTX100743 TMPRSS2 antibody [N2C3] Rb pAb WB

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