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How can recombinant proteins help researchers study SARS-CoV-2?

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How can recombinant proteins help researchers study SARS-CoV-2?

Although coronaviruses have long circulated throughout human populations, the study of these viruses has intensified over the last two decades, due to the rise of novel coronaviruses that have greatly impacted human health. The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle East respiratory syndrome-related coronavirus (MERS-CoV) in 2012, and the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, has emphasized the importance of understanding the fundamental mechanisms by which these viruses cause disease.


SARS and SARS-CoV-2 initiate cell entry by binding to the angiotensin converting enzyme 2 (ACE2) protein via their trimeric spike (S) glycoprotein. This spike protein comprises two functional subunits, S1 and S2. The S1 subunit encompasses four domains specified as S1A-S1D and is involved in binding to the host cell receptor attachment to the cell; S2 is utilized for fusion between the viral and cellular membranes. The S1B domain, or Receptor Binding Domain (RBD), is of particular importance, as this is the domain that directly binds to ACE2 and facilitates membrane fusion (1). Currently, there is a very limited toolset to detect antibodies against the spike proteins, which will be critically important both for further understanding of the virus function and for developing therapeutics for COVID- 19.

Cell Signaling Technology (CST) has developed a collection of recombinant proteins, corresponding to different domains of the SARS-CoV-2 Spike protein and the host receptor ACE2, that can be used to study SARS-CoV-2. The proteins are available with different tag configurations (e.g., 8xHis, murine Fc) allowing for the flexibility to be used in a variety of assay formats. Researchers can therefore take advantage of the multiple Spike S1-NTD recombinant proteins, which are critical for studying SARS-CoV-2 interactions with ACE2. CST offers a recombinant protein corresponding to the full-length Spike protein ectodomain engineered to express as a trimer, which reflects the native configuration of the Spike protein on the viral surface, as well as multiple forms of the Spike receptor-binding domain (RBD) protein, enabling substantial flexibility in assay design. The trimeric protein can be used as a component of an ELISA assay for detecting COVID-19 seroconversion (2), which allows for a quick and reliable measurement of SARS-CoV-2 antibody titers. The SARS-CoV-2 Spike RBD (multimeric) (319-591) Recombinant Protein (8xHis-Tag) #17862, a specially engineered version of the spike protein RBD, has demonstrated a higher avidity for the ACE2 receptor than RBD proteins expressed recombinantly as a monomer. CST has also generated a biotinylated form of the multimeric spike RBD, which offers a reproducible and predictable way to attach the protein to a surface across many different assay platforms. This makes it an ideal option for inhibitory assays where the goal is to prevent the binding between the SARS-CoV-2 spike protein and ACE2 (3) thereby preventing viral entry into the cell. The ACE2 and spike RBD recombinant proteins may also be used in the development of peptide inhibitors, characterizing antibody cross-reactivity, or examining binding kinetics between the virus and the host receptors.

Given the potential for inducing multiple severe conditions, scrutinizing SARS-CoV-2, its protein components, and its interactions with ACE2 is of critical importance. Recombinant proteins toward these components are extremely useful reagents to those undertaking this research, which will ultimately provide us the tools needed to identify and combat these viral infections.



  1. Wang, C. et al. A human monoclonal antibody blocking SARS-CoV-2 infection. Commun. 11, 1–6 (2020).
  2. Amanat, F. et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. Med. (2020). doi:10.1038/s41591-020-0913-5
  3. Nie, J. et al. Establishment and validation of a pseudovirus neutralization assay for SARS-CoV-2. Microbes Infect. 9, 680–686 (2020).

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