Viruses are intracellular parasites that hijack cell metabolism to their advantage. Sometimes the effects of the virus are rather unusual, such as the appearance of large, branched tentacles on the surface of the cell.
When a virus enters a cell, it completely disrupts the established order. Coronavirus is no exception. In a very dense study, intended to appear soon in Cell, scientists studied the changes in phosphorylation of cellular proteins during an infection with SARS-CoV-2.
This work was carried out in vitro on epithelial cells in culture. Coronavirus infection increases or decreases the activity of kinases, the enzymes responsible for phosphorylation, with sometimes strange consequences in the shape of the cell. Indeed, one of the changes induced by SARS-CoV-2 infection results in the appearance of tentacles on the surface of cells.
When the coronavirus infects a cell, it appropriates cellular enzymes for transcription and translation. As expected, the researchers observed a decrease in the number of cellular proteins in favor of viral proteins. In addition to the increasing amount of viral proteins, the virus also modifies the phosphorylation sites of cellular proteins.
The researchers identified 27 proteins encoded by the coronavirus capable of interacting with 332 cellular proteins. Among these, 40 see their phosphorylation site change during infection. And these changes are not without consequences.
One of the most visual examples concerns the kinase CK2 (casein kinase 2). This enzyme is involved in many regulatory pathways and phosphorylates, among others, actin and myosin, proteins of the cytoskeleton. When the coronavirus infects a cell (here the human epithelial cell line Caco-2), the activity of CK2 skyrockets. The cell then develops tentacle-like growths.
These protrusions, called filopods, are also present in healthy cells, but on infected cells, they are much longer and branched. Images taken by electron microscopy show that they are covered with virions. Researchers believe the virus uses them to help spread them.
This phenomenon has already been documented in other viral infections such as AIDS, herpes and rotaviruses (responsible for gastroenteritis). The presence of these tentacles seems essential for the spread of the virus. Indeed, the researchers inhibited CK2 and therefore the filopods, with Silmitaserib.
This molecule is the subject of clinical studies as a treatment for certain cancers in which tumor cells overexpress CK2. In the case of SARS-CoV-2, the researchers observed a possible antiviral activity. In addition, the Taiwanese biotechnology company Senwha Biosciences is already carrying out experiments to confirm the antiviral effect of Silmitaserib.