Emerging SARS-CoV-2 Variant of Concern

The COVID-19 pandemic is ongoing, with the global coronavirus 2019 disease (also known as the COVID-19 disease) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus.

Since the COVID-19 pandemic began in 2019, scientists have continued to be interested in how quickly the novel SARS-CoV-2 can mutate as it spreads.

Mutations induced by the virus have the potential to make it deadlier and more infectious, increasing the speed at which the virus spreads and making it harder to control, all the while posing a significant risk to public health.

The South African SARS-CoV-2 mutant, known as the 20C/501Y.V2 or B.1.351 lineage, is one such variant. It is highly transmissible and is known to have originated in South Africa.

This variant can be primarily characterized by three key mutations. These mutations make the viral strain more virulent, enhancing its ability to bind to human cellular receptors.

These three key mutations (K417N, E484K, N501Y) have been found to be present on the SARS-CoV-2 spike protein (S) whereby:

  1. K417N mutation is a lysine to asparagine substitution at amino acid position 417 in the S protein.
  2. E484K mutation is a glutamic acid to lysine substitution at amino acid position 484 in the S protein.
  3. N501Y is an asparagine to tyrosine substitution at amino acid position 501 in the S protein.

2019-nCoV spike protein RBD (K417N, E484K, N501Y)

Catalog No. C19SD-G232H

Recombinant 2019-nCoV Spike protein S1 subunit, RBD (K417N, E484K, N501Y) (319-541) can be expressed in CHO cells using a C-terminal His tag.

The South African variant of SARS-CoV-2 was identified in South Africa in November 2020. Since then, this highly virulent variant has spread rapidly across America, Europe, Australia, and Asia, resulting in it being one of the most studied variants of the SARS-CoV-2 virus.

This variant has been a cause for concern for the global scientific community because the multiple mutations found on its spike (S) protein make it highly aggressive while simultaneously potentially reducing the effectiveness of vaccines.

This factor may also negatively affect the antibody neutralization efficacy of vaccines that have been developed based on earlier SARS-CoV-2 strains and which are currently being administered to the public.

Scientists at SignalChem have been closely monitoring rapid mutations in the SARS-CoV-2 virus, working to respond to the growing challenges posed by manufacturing effective recombinant versions of SARS-Cov-2 variants.

The SARS-CoV-2 (501Y.V2 variant) has been engineered with mutations at key sites in the RBD (K417N, E484K, and N501Y). This combination of E484K, K417N, and N501Y leads to the highest degree of conformational modifications of RBD when bound to ACE2 when analyzed in comparison with the E484K or N501Y mutation alone.

E484K and N501Y enhance the affinity of RBD for ACE2, while the charge switch due to E484K results in the formation of favorable circumstances for binding.

The 2019-nCoV spike protein RBD (K417N, E484K, N501Y) has been expressed in CHO cells and this has been subjected to rigorous QC QA tests in order to quantify its activity. These tests have been performed via functional ELISA and purity using densitometry.

This recombinant variant is ready to be used in COVID-19 research. It is also highly suited to the development of SARS-CoV-2 diagnostic kits and anti-viral therapeutics, with the potential to speed up vital research against new coronavirus variants.

Binding ability measured in a functional ELISA. 2019-nCoV spike protein RBD (K417N, E484K, N501Y) binds to immobilized human ACE2 (19-740) protein (A51C2-G341F).

Figure 1. Binding ability measured in a functional ELISA. 2019-nCoV spike protein RBD (K417N, E484K, N501Y) binds to immobilized human ACE2 (19-740) protein (A51C2-G341F). Image Credit: SignalChem Biotech Inc.

SignalChem: A global leader in cell signaling

SignalChem is a world leading provider of cell signaling and protein engineering solutions. The company has been undertaking research into the new coronavirus since its initial outbreak.

SignalChem’s scientists have invested significant resources in better understanding SARS-CoV-2’s protein interaction map in order to successfully engineer active recombinant SARS-CoV-2 and human proteins.

SignalChem’s primary goal is to provide other researchers with these essential pieces of the puzzle, many of which are central to drug discovery research projects worldwide.

Utilizing AI drug development software and advanced engineering technology, SignalChem has already initiated projects aiming to develop expression systems of key COVID-19 related proteins. These include hot drug targets such as non-structural proteins (NSPs) and proteases.

All of these catalytically active proteins can be considered fully functional and suitable for use in an array of research into the development of drugs directed against coronavirus infections such as SARS-CoV-2.

About SignalChem Biotech Inc.

SignalChem is a biotech company focused on the research, development, and production of innovative and high-quality human recombinant cell signaling products.

Throughout the years, Signalchem has capitalized on its core expertise in cellular signaling, molecular biology, and protein biochemistry to generate more than 2,000 functional protein products and has established itself as the leader in the industry to produce highly active human recombinant signaling enzymes, especially protein kinases, disease-related mutant kinases, lipid kinases, epigenetic enzymes, ubiquitination-related enzymes, and neurodegenerative disease-related enzymes and proteins.

SignalChem strives to support scientists in academia, pharma and biotech companies around the world by creating effective research tools to advance the basic research in life sciences and to facilitate the efforts in drug discovery and development.

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Last updated: Mar 16, 2021 at 6:59 AM


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