Researchers identify potential coronavirus vaccine and therapy targets
Researchers show that antibodies that can neutralize the virus that causes SARS can reduce how well the new coronavirus infects cells in laboratory studies. They also use an approved drug to reduce virus entry into cells.
The new coronavirus, SARS-CoV-2, is a type of virus called an enveloped RNA virus.
This means that its genetic material is encoded in single-stranded RNA molecules surrounded by a cell membrane taken from the cell that it last infected.
When enveloped viruses infect a cell, they do this using a two-stage process.
The first step involves making a connection with a receptor on the surface of the target cell. The second is fusion with a cell membrane, either on the surface of the cell or at an internal location.
In the case of coronaviruses, the first step requires that specific proteins in the viral envelope, called spike (S) proteins, undergo a biochemical modification. This step is called S protein priming.
The enzymes responsible for S protein priming are potential therapeutic targets as inhibiting their mechanism may prevent a virus from being able to enter a cell.
“Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets,” write the authors one of the new papers in Cell.
The senior study author is Stefan Pöhlmann, a professor for Infection Biology at Georg-August-University and Head of the Infection Biology Unit of the German Primate Center, both in Göttingen in Germany.
Pöhlmann and his colleagues show evidence that the SARS-CoV-2 S protein binds to the same receptor as the SARS virus S protein. The receptor is called angiotensin-converting enzyme 2 or ACE2.
In fact, an earlier paper in the journal Nature had already implicated ACE2 as the receptor that allows SARS-CoV-2 to infect cells.
In addition to providing further evidence of ACE2’s role, Pöhlmann and the team also saw that, like SARS-CoV, the new coronavirus S protein uses an enzyme called TMPRSS2 for S protein priming.
Importantly, they showed that “camostat mesylate, an inhibitor of TMPRSS2, blocks SARS-CoV-2 infection of lung cells.”
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Journal of Biomolecules and Biochemistry