COVID-19 Hijack Mechanism Halted By Repurposed Drugs

Molecular responses - the proteins and pathways of the host lung cells that alter upon infection by the SARS-CoV-2, provide insights into disease pathology, thereby helping to design new therapeutic targets to block COVID-19, as per multi-group collaborative research involving the National Emerging Infectious Disease Laboratories (NEIDL), the Center for Regenerative Medicine (CReM), and the Center for Network Systems Biology (CNSB), at Boston University School Of Medicine. A type of protein modification called "phosphorylation" becomes aberrant in the infected lung cells as the SARS-CoV-2 virus causes abnormal changes in protein phosphorylation. This helps the virus to multiply and eventually destroy the cells. The destruction of infected cells may result in widespread lung injury. The coronavirus does this by exploiting the cell's core resources, which are required for the cell's normal growth and function.

COVID-19 Hijack Mechanism:

"The virus uses these resources to proliferate while evading attack by the body's immune system. In this way new viruses form which subsequently exit the exhausted and brutally damaged lung cells, leaving them to self-destruct. These new viruses then infect other cells, where the same cycle is repeated," explains the corresponding author Andrew Emili, Ph.D., professor of biochemistry at BUSM.

The researchers examined lung alveolar cells from one to 24 hours after infection with SARS-CoV-2 to get a clear picture of the various mechanism happening at different time points, using a mass spectrometer. Abundance of many proteins and phosphorylation events were observed in infected cells as compared to normal ones.

"Moreover, our data also showed that the SARS-CoV-2 virus induces a significant number of these changes as early as one-hour post-infection and lays the foundation for a complete hijack of the host lung cells," adds Elke Muhlberger, Ph.D., associate professor of microbiology and principal investigator at the NEIDL.

This in-depth study of damaged cells and their pathway identified almost 18 pre-existing clinically approved drugs (developed originally for other medical conditions/diseases) that can be potentially repurposed for use towards COVID-19 therapy. These drugs thus show exceptional promise to block the proliferation of the SARS-CoV-2 in lung cells.

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Source-Medindia