AMPK: A target to block the replication of SARS-COV-2
In our cells, a protein called AMPK plays a role of energy conductor. When it activates, it slows down energy consuming paths, such as lipid and protein synthesis, and it stimulates internal recycling mechanisms, including autophagy, a process by which the cell “cleanses” its waste to draw nutrients.
But some viruses, such as SARS-COV-2, responsible for COVID-19, divert this system to their advantage. They block autophagy and accumulate lipid droplets in viral factories allowing to maintain viral replication. This strongly promotes their multiplication.
In an article published in the journal Journal of Virologyscientists have explored a promising track to block this diversion: activate the AMPK to restart the natural defenses of the cell.
MK-8722: a promising antiviral candidate against the variants of SARS-COV-2
The MK-8722 molecule is a specific activator of the AMPK. Scientists have shown, in the laboratory, that the MK-8722 has a strong capacity to effectively block the infection of alpha and icicron variants of SARS-COV-2 in epithelial cells Vero76 models and Calu-3 human epithelial cells with a micromolar concentration. Even administered 4 hours after infection, treatment with the MK-8722 remains effective.
The MK-8722 works by reactivating autophagy, which causes the destruction of newly synthesized viral proteins and the reduction of lipid metabolism facilitating the elimination of the virus. In addition, treatment increases the response to type I interferon (IFN-I), a key molecule of antiviral control mediated by our immune system. Finally, this treatment with the MK-8722 does not decrease and even slightly increases the response of T CD8+ lymphocytes specific to SARS-COV-2, immune cells induced by vaccination.
By activating the AMPK, the MK-8722 acts as an effective antiviral against the SARS-COV-2 infection, even after exposure, opening the way for preclinical trials aimed at inhibiting viral replication and improving patient symptoms.
