Manufacturing Effective Recombinant SARS-CoV-2 Mutants

Viruses have the ability to change and adapt through mutation, creating new variants of themselves over time. The COVID-19 pandemic has been caused by the novel SARS-CoV-2, which is part of a large family of RNA viruses.

Severe Acute Respiratory Syndrome (SARS) Coronavirus 2 (SARS-CoV-2) derives its name from the crown-like spikes (Spike proteins) found on its surface.

Global travel, coupled with the virus’s rapid rate of transmission, has provided sufficient space for the virus to mutate rapidly, resulting in the creation of multiple variants.

Scientists are continually using genetic screening tools to analyze the virus to closely monitor evolving variants, particularly those involving changes to the Spike (S) protein on the surface of the virus.

Spike (S) protein is one of the virus’s primary means of binding to a range of cellular receptors, including TMPRSS2, AXL, and ACE2. Mutated S protein has the potential to become more virulent, increasing the rate of infection.

A new variant of the SARS-CoV-2 was discovered by scientists in the United Kingdom in November 2020. This mutant - B.1.1.7 lineage - features mutation N501Y at one of the six major contact residues in the receptor-binding domain responsible for ACE2 binding.

This mutation presents itself on the SARS-CoV-2 spike protein (S) in instances where:

  1. N501Y is an asparagine (an amide containing amino acid) to tyrosine (a phenol containing amino acid) substitution at amino acid position 501 in the S protein.

2019-nCoV spike protein RBD (N501Y)

Catalog No. C19SD-G231H

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

This Spike protein mutation has naturally occurred more than three times naturally, indicating that it provides the virus with a robust evolutionary advantage.

The mutation alters the biding potential of the Spike (S) protein’s receptor-binding domain (RBD), enhancing its ability to bind to human cell receptors.

It has also been hypothesized that this key mutation helps the virus to avoid the host’s immune system response by evading neutralizing antibodies.

This particular mutation poses problems for vaccines currently in circulation because these vaccines were developed to be effective against initial SARS-CoV-2 variants.

Scientists at SignalChem have been quick to respond to the requirements of the global scientific community, leading in the manufacture of effective recombinant SARS-CoV-2 mutants designed to expedite research into these emerging variants.

The SARS-CoV-2 (N501Y variant) has been engineered with mutations at key sites in the RBD subunit (N501Y) because this combination offers the highest degree of conformational modifications of RBD when bound to ACE2 at one of the six major contacts residues in the receptor-binding domain linked to ACE2 binding.

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

This recombinant variant is an effective candidate that is available for use in a range of COVID-19 research, including the development of anti-viral therapeutics and SARS-CoV-2 diagnostic kits that are able to support and enhance research into emerging variants of the virus.

Binding ability measured in a functional ELISA. Compared to 2019-nCoV spike protein RBD (C19SD-G241H), 2019-nCoV spike protein RBD (N501Y) exhibits increased binding potency for immobilized human ACE2 (19-740) protein (A51C2-G341F).

Figure 1. Binding ability measured in a functional ELISA. Compared to 2019-nCoV spike protein RBD (C19SD-G241H), 2019-nCoV spike protein RBD (N501Y) exhibits increased binding potency for immobilized human ACE2 (19-740) protein (A51C2-G341F). Image Credit: SignalChem Biotech Inc.

SignalChem: A global leader in cell signaling

SignalChem is a global leader in protein engineering and cell signaling. The company has been conducting research into the novel coronavirus since the initial outbreak of the virus, with its scientists investing substantial time and resources into better understanding the protein interaction map of SARS-CoV-2.

The primary aim of this work is to successfully engineer active recombinant human and SARS-CoV-2 proteins.

SignalChem aims to provide researchers worldwide with the building blocks essential for drug discovery research projects.

By employing advanced engineering technology along with AI drug development software, SignalChem has already begun work on numerous projects and the company is developing expression systems of key COVID-19 related proteins, including hot drug targets such as proteases and non-structural proteins (NSPs).

These catalytically active proteins have been described as fully functional and are available for use in research into the development of drugs directed against SARS-CoV-2 and related coronavirus infections.

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 6:58 AM


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