Cells pirated by SARS-CoV-2, an unique coronavirus that triggers the COVID-19 illness, grow arm-like extensions, or filopodia, which may explain fast viral spread throughout the body.
SARS-CoV-2 viruses noticeable on a cell with filopodia. Image credit: Elizabeth Fischer, Miscroscopy Unit NIH/ NIAID.
” Viruses are unable to reproduce and spread on their own: they need an organism to carry, reproduce, and transfer them to additional hosts,” explained study very first author Dr. Mehdi Bouhaddou of Gladstone Institutes and the University of California San Francisco and coworkers.
” To facilitate this process, infections require to take control of their host cell’s equipment and control it to produce new viral particles. In some cases, this hijacking disrupts the activity of the host’s enzymes and other proteins.”
” As soon as a protein is produced, enzymes can change its activity by making chemical modifications to its structure.”
” For instance, phosphorylation— the addition of a phosphoryl group to a protein by a type of enzyme called a kinase– plays a critical function in the regulation of many cell processes, consisting of cell-to-cell communication, cell development, and cell death.”
” By changing phosphorylation patterns in the host’s proteins, a virus can potentially promote its own transmission to other cells and, ultimately, other hosts.”
The researchers used mass spectrometry to examine all host and viral proteins that showed changes in phosphorylation after SARS-CoV-2 infection.
They determined that 40 of the 332 human proteins that engage with SARS-CoV-2 were substantially differentially phosphorylated.
In addition, they recognized 49 human kinases, out of a total of 518, that showed changes– either upregulation or downregulation– of phosphorylation activity.
The most highly hijacked kinases include casein kinase II (CK2), kinases within the p38/ MAP kinase (p38/ MAPK) path, cyclin-dependent kinases (CDKs) and phosphatidylinositol 5-kinase (PIKFYVE), all of which fall within a set of cell signaling pathways.
” The virus avoids human cells from dividing, keeping them at a particular point in the cell cycle. This supplies the infection with a relatively stable and appropriate environment to keep duplicating,” said co-lead author Dr. Pedro Beltrao, a scientist at the EMBL’s European Bioinformatics Institute.
One of the essential findings is that infected cells display long, branched, arm-like extensions, or filopodia.
These structures might assist the virus reach nearby cells in the body and advance the infection, but further study is required.
SARS-CoV-2 (stained for N-protein in red) was found inside called filopodia made from actin cytoskeleton filaments (white) as shows up on these tiny images. Image credit: Robert Grosse, CIBSS, University of Freiburg.
” The distinct visualization of the extensive branching of the filopodia as soon as again illuminates how understanding the biology of virus-host interaction can light up possible points of intervention in the illness,” said co-lead author Dr. Nevan Krogan, Director of the Quantitative Biosciences Institute the University of California San Francisco and Senior Private Investigator at Gladstone Institutes.
” Kinases possess certain structural functions that make them good drug targets. Drugs have already been developed to target a few of the kinases we determined, so we advise medical researchers to check the antiviral effects of these drugs in their trials,” Dr. Beltrao said.
In some patients, COVID-19 causes an overreaction of the immune system, leading to swelling.
The group determined 87 drugs authorized by the Food and Drug Administration (FDA) or ongoing clinical trials that target the kinases of interest.
Seven of these substances, primarily anticancer and inflammatory disease substances, showed potent antiviral activity in laboratory experiments.
” Our data-driven approach for drug discovery has actually recognized a new set of drugs that have terrific possible to fight COVID-19, either by themselves or in mix with other drugs, and we are thrilled to see if they will help end this pandemic,” Dr. Krogan said
” We expect to build upon this work by checking numerous other kinase inhibitors while identifying both the underlying pathways and extra potential rehabs that might intervene in COVID-19 efficiently,” stated co-lead author Teacher Kevan Shokat, a scientist at the University of California San Francisco.
Mehdi Bouhaddou et al The Worldwide Phosphorylation Landscape of SARS-CoV-2 Infection. Cell, published online June 28, 2020; doi: 10.1016/ j.cell.202006034
This post is based upon press-releases provided by the European Bioinformatics Institute and the University of Freiburg.