SARS‐CoV‐2 Therapy Targets

s

s

Overview

At the end of 2019, a coronavirus had again jumped species to infect humans. Referred to as SARS‐CoV‐2, due to similarity with SARS-CoV that broke out in 2003, it leads to a contagious respiratory and vascular disease labeled COVID-19. However, in severe contrast to SARS, COVID-19 led to a pandemic. Some published work has focused on the nucleoprotein as a second avenue to control the virus.

Coronavirus Components

Coronaviruses are positive-sense, single-stranded RNA viruses made up four structural proteins:

• S (spike)
• E (envelope)
• M (membrane)
• N (nucleocapsid)

The S, E, and M proteins are the viral envelope, while the N protein stores the RNA genome. Additionally, up to 16 nonstructural proteins have regulatory and enzymatic support functions.

Nucleocapsid Protein

The N protein forms the nucleocapsid. It is made up of two separate domains; an N-terminal and a C-terminal domain, both able to bind RNA. During virion assembly, the N protein is extensively phosphorylated which has been suggested to facilitate preferential binding of the viral RNA. It also interacts with components of the replicase complex and the M protein (Perlman and Netland 2009). Finally, the N protein has also been suggested to interfere with stress granule formation to negate host antiviral responses and enhance viral replication (Cascarina and Ross 2020).

Immune Response

Whilst investigating SARS-CoV patients, it was discovered that antibodies were raised against the N protein. These had higher sensitivity and longer half-lives than antibodies to other SARS-CoV proteins (Tan et al. 2004). This is also true for SARS-CoV-2 infections where patient derived IgA, IgM, and IgG antibodies bound recombinant nucleocapsid protein (Guo et al. 2020, Zeng et al. 2020). These and other data have led to the suggestion that the N-protein should be a target for vaccine development (Dutta et al. 2020)

Coronaviruses in Veterinary Species

While coronaviruses have only recently gained notoriety for causing illness in humans, they have been a concern for animal welfare for much longer. Find out more about the impact they have on veterinary and companion animal species, particularly for swine, cattle, and felines.

Antibodies to Coronaviruses

Bio-Rad offers an antibody reactive with feline coronavirus nucleocapsid protein. Clone FIPV3-70, available in purified format, is suitable for use in ELISA, flow cytometry, immunofluorescence, immunohistology on frozen and paraffin (with pretreatment) sections, and western blotting. It has been reported that clone FIPV3-70 recognizes the SARS-CoV-2 core protein.

COVID-19 Research Support

Bio-Rad is committed to helping find a cure to COVID-19 and provides a full spectrum of research support, including:

Custom generation of COVID research specific antibodies

The rapid custom recombinant monoclonal antibody generation service utilizes HuCAL® phage display technology to provide highly specialized antibodies for coronavirus research, diagnostic testing, plus vaccine and therapeutic development.

Biotherapeutic antibodies for use in COVID specific clinical trials

Bio-Rad’s range of anti-tocilizumab antibodies can be used in COVID research and therapeutic development that is focused on the IL-6 inhibitor tocilizumab (Actemra, RoActemra), which has been used in clinical trials on patients with severe COVID-19 pneumonia. These biotherapeutic recombinant, anti-idiotypic antibodies are robust, reliable, and ready-made for bioanalysis and drug monitoring.

Antibodies to profile the immune response to COVID

The catalog of ready-to-order antibodies covers the key immune research area of innate and adaptive immunology reagents, such as antibodies to pattern recognition receptors (PRRs) and an extensive portfolio of B and T cell markers. The primary immune response to COVID-19 can be measured with Bio-Rad’s wide selection of anti-human IgA, IgG, and IgM antibodies.

Accessory reagents for COVID research

In addition to our catalog of antibodies for COVID research use, we offer a wide range of useful buffers, reagents, and accessory products:

• ELISA
• Flow cytometry
• Western blotting
• Buffers and accessory reagents

References

• Cascarina SM and Ross ED (2020). A proposed role for the SARS‐CoV‐2 nucleocapsid protein in the formation and regulation of biomolecular condensates. FASEB J. 34, 9832−9842.
• Dutta NK et al. (2020). The nucleocapsid protein of SARS-CoV-2: a target for vaccine development. J Virol. 94(13), e00647−20.
• Guo L et al. (2020). Profiling early humoral response to diagnose novel coronavirus disease (COVID-19). Clin Infect Dis. 71(15), 778−785.
• Perlman S and Netland J (2009). Coronaviruses post-SARS: update on replication and pathogenesis. Nat. Rev. Microbiol. 7(6), 439−450.
• Tan YJ et al. (2004). Profiles of antibody responses against severe acute respiratory syndrome coronavirus recombinant proteins and their potential use as diagnostic markers. Clin Diagn Lab Immunol. 11(2), 362−371.
• Zeng W et al. (2020). Biochemical characterization of SARS-CoV-2 nucleocapsid protein. Biochem Biophys Res Commun. 527(3), 618−623.