RNA-Dependent RNA Polymerase (RdRp): An Essential Enzyme in the Life Cycle of SARS-CoV-2

There are currently no effective antiviral vaccines or drugs approved for the management of COVID-19 infections resulting from the novel SARS-CoV-2 virus.

Thanks to the research community’s previous experience dealing with other members of the coronavirus family (for example, SARS-CoV and MERS-CoV), it is known that the inhibition or modification of key viral functional proteins such as PLpro (NSP3), RdRp (NSP12) and helicase (NSP13) can effectively control the infection, because these proteins are crucial for viral transcription and replication.

The RNA-dependent RNA polymerase (RdRp) is one of the most important enzymes employed by SARS-CoV-2 in viral RNA replication. Without host cell homologs, potent RdRp antivirals can be developed for use against the virus, lessening off-target side effects against host proteins. This results in RdRp being a more potent and safer target for the treatment of COVID-19.

RdRp (NSP 12) (C19RP-G241H)

In one example, recombinant 2019-nCoV RNA-dependent RNA polymerase (RdRp) was expressed in E.coli cells using a C-terminal His tag.

SARS-CoV-2’s replication is mediated by RNA-dependent RNA polymerase (RdRp, also known as NSP12). This is the core component of a replication/transcription catalytic complex of viral nonstructural proteins (NSP).

RdRp does have minimal activity on its own, but adding nsp7 and nsp8 cofactors results in enhanced template binding and processivity, significantly increasing RdRp’s capacity for replicating long RNA.

It has been proposed that RdRp could be the target of a class of antiviral drugs that are nucleotide analogs (including remdesivir), primarily due to its vital role in the life cycle of RNA viruses. Remdesivir has already been assessed against a clinical isolate of SARS-CoV-2, demonstrating a half-maximal effective concentration (EC50) of 0.77 μM and a selectivity index of 129.87 (Vero E6 cells).

Since the FDA authorized the use of remdesivir for the emergency treatment of COVID-19, a total of 26 clinical trials have been approved around the world, aiming to demonstrate its therapeutic potential. A total of 16 of these trials are currently in phase III.

RNA polymerase activity of RdRp (SignalChem Catalog No. C19RP-G241H), as detected in a bioluminescence assay.

Figure 3. RNA polymerase activity of RdRp (SignalChem Catalog No. C19RP-G241H), as detected in a bioluminescence assay. Image Credit: SignalChem Biotech Inc.

As a world leader in protein engineering and cell signaling, SignalChem has been researching the new coronavirus since the recent outbreak began. SignalChem’s scientists have invested considerably in better understanding the protein interaction map of SARS-CoV-2; their goal being the successful engineering of active recombinant SARS-CoV-2 and human proteins.

SignalChem’s goal is to offer other researchers these important pieces of the puzzle, which can help colleagues around the world to develop their own drug discovery research projects.

Advanced engineering technology and AI drug development software have allowed SignalChem to initiate projects already, aiming to develop expression systems of key COVID-19 related proteins. For example, hot drug targets such as non-structural proteins (NSPs) and proteases.

Catalytically active proteins such as these are commonly described as fully functional and suitable for use in research projects and the development of drugs directed against SARS-CoV-2, as well as other 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: Nov 6, 2020 at 4:55 AM

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