Researchers have shown that the new coronavirus diverts proteins into its target cells, which could cause them to form long arm-like extensions to reach neighboring cells and advance the infection, a discovery that led to the identification of clinically approved drugs that may disrupt the process.
Scientists, including those from the European Institute for Bioinformatics at EMBL (EMBL-EBI) and the University of California at San Francisco (UCSF) in the United States, noted that viruses, including the new SARS-CoV-2 coronaviruses take control of the machinery of host cells and manipulate them to produce new viral particles.
They said that this diversion sometimes interferes with the activity of host proteins and other important molecules such as enzymes, which alter the activity of proteins by making chemical changes to its structure.
In the study, published Sunday in the journal Cell, the scientists analyzed all of the host and viral proteins that showed changes in an enzymatic process called phosphorylation after infection with SARS-CoV-2.
They explained that in phosphorylation, there is the addition of a “ phosphoryl group ” to a protein by a type of enzyme called kinase, which plays a key role in the regulation of many cellular processes, including cell-to-cell communication, cell growth and cell death.
According to the researchers, by modifying the phosphorylation patterns of host proteins, a virus can potentially promote its own transmission to other cells and, possibly, to other hosts.
They discovered that 12% of the host proteins that interact with the virus have been modified.
The scientists also identified the kinases most likely to regulate these changes and suggested that these enzymes are potential targets for drugs to stop the activity of the virus and treat COVID-19.
“The virus prevents human cells from dividing, keeping them at a particular point in the cell cycle. This provides the virus with a relatively stable and adequate environment to continue replicating, “said Pedro Beltrao, group leader at EMBL-EBI and co-author of the study.
One of the main conclusions of the study, scientists say, is that cells infected with SARS-CoV-2 have long, branched, arm-like extensions or filopods, which can help the virus reach neighboring cells. of the body and advancing the infection.
However, according to the researchers, more study is needed to validate these results.
“The distinct visualization of the extended branching of filopods elucidates once again how understanding the biology of virus-host interaction can shed light on possible points of intervention in the disease,” said Nevan Krogan, co-author of the UCSF study.
In the study, the researchers also identified dozens of drugs approved by the Food and Drug Administration of the United States (FDA) which target the kinases of interest.
They said that seven of these compounds, mainly anti-cancer compounds and inflammatory diseases, demonstrated potent antiviral activity in laboratory experiments.
“Our data-driven approach to drug discovery has identified a new set of drugs that have great potential to fight COVID-19, either alone or in combination with other drugs, and we are delighted to see s ‘They will help end this pandemic,’ said Krogan.