Potentially fatal pathogens such as SARS-CoV, SARS-CoV-2, and MERS-CoV rely on host cells for infection and replication. Virus-host cell interaction is critical if the virus is to successfully enter these cells.
Cell entry of the novel coronavirus is reliant on binding the viral spike (S) protein to the host cell proteases TMPRRS2 and ACE2. Advances in research aimed at tackling the deadly SARS-CoV-2 virus have suggested that the virus interacts with the transmembrane protease TMPRSS2, facilitating its entry into the cell.
Therefore, successfully inhibiting this interaction could offer a viable therapeutic intervention against the COVID-19 infection.
TMPRSS2 active (T51S2-E361H)
Human cell entry of coronaviruses such as SARS-CoV-2 relies on binding the viral spike (S) protein to a particular cellular receptor (ACE2) and then commencing S protein activation by proteolytic cleavage. The transmembrane protease serine 2 (TMPRSS2) is one of a pair of host cell proteases accountable for S protein priming leading to membrane fusion.
Recent studies have found that SARS-CoV-2 infection is more enhanced in TMPRSS2-expressing cells. Both TMPRSS2 and ACE2 are highly co-expressed in nasal epithelial cells with genes linked to innate immunity. This combination of factors clearly demonstrates the important role of TMPRSS2 in viral invasion.
In contrast to the other protease (furin), TMPRSS2 has no identified indispensable cellular functions. This, and the availability of inhibitors, make this an attractive target for the treatment or prevention of respiratory viral infections.
The U.S. National Library of Medicine cites fourteen currently authorized clinical trials aiming to assess TMPRSS2 as either a therapeutic target or a prognostic biomarker for the treatment of COVID-19. A clinically proven serine protease inhibitor - camostat mesylate - is being investigated in a number of these trials, due to its therapeutic potential against SARS-CoV-2.
A recent report by Hoffmann et al. stated that camostat mesylate was found to partially block SARS-CoV-2 S protein-driven entry into TMPRSS2-expressing human lung cells, while having no effect on TMPRSS2-knockout cells.
Two other TMPRSS2 inhibitors are currently under investigation: nafamostat, which is able to inhibit the SARS-CoV-2 membrane fusion at a concentration under one-tenth that of camostat; and the FDA-approved mucolytic cough suppressant bromhexine, mixed with hydroxychloroquine, the competitive inhibitor of viral-ACE2 binding.
As a global leader in protein engineering as well as cell signaling, SignalChem, has been researching the latest coronavirus since the outbreak began. Its scientists have invested considerable resources in better comprehending the protein interaction map of SARS-CoV-2, aiming to successfully engineer active recombinant SARS-CoV-2 and human proteins. SignalChem aims to provide other organizations with these vital pieces of the puzzle, which are indispensable in drug discovery research projects across the globe.
SignalChem has employed advanced engineering technology alongside AI drug development software to initiate projects, developing expression systems of key COVID-19 related proteins involving hot drug targets; for example, proteases and non-structural proteins (NSPs).
Catalytically active proteins such as these can be described as fully functional. They are ready to be used in a variety of research projects and in 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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