An international team of scientists has discovered a mechanism by which Sars-CoV-2 takes control of human cells – and that currently existing drugs have the power to stop it.
An international team of scientists led by the Molecular Biology Laboratory of the European Bioinformatics Institute was able to explain how the “hijacking” of healthy cells by Sars-CoV-2 occurs and also pointed out seven existing drugs that can prevent the mechanism. The study was published on June 23 in the journal Cell.
“Our data-driven approach for drug discovery has identified a new set of drugs that have great potential to fight COVID-19, either by themselves or in combination with other drugs, and we are excited to see if they will help end this pandemic,” study co-author Nevan Krogan, a molecular biologist at the University of California, San Francisco, said in a statement.
According to the scientists, an enzyme called kinase must be the main target of drugs that aim to interrupt the activity of the virus and treat Covid-19. So they have analyzed dozens of drugs that deal with this enzyme and are either approved by the United States Food and Drug Administration (FDA), or are being used in tests. Among the drugs, they found seven that showed potent antiviral activity in laboratory experiments. The drugs are mainly linked to compounds against inflammatory diseases and cancer.
Despite being very powerful, viruses are unable to replicate or spread on their own: they need a host to reproduce. Once they enter our body, these microorganisms try at all costs to take control of the mechanisms of our cells, taking advantage of them to be able to produce new viral particles. During this “hijacking”, the virus can even modify the activity of the host enzymes and proteins.
Phosphorylation – the addition of a phosphoryl group to a kinase enzyme – is an example of a process that can be changed to benefit the virus. This is because this mechanism is associated with the regulation of many cellular processes, such as communication between cells, their growth, and even their death. By changing the pattern of phosphorylation, the virus may be able to replicate to other cells and even to other hosts.
With that in mind, the scientists used a tool called mass spectrometry to assess how phosphorylation of viral and host proteins was modified after infection with Sars-CoV-2. They found that 12% of the host proteins that interacted with the virus underwent changes. They also managed to identify the kinases that are most likely to regulate those changes.
In addition, the researchers concluded that the new coronavirus affects not only cell division, but also the shape of the cell. One of the main findings of the study is that the infected cells have long and branched extensions, similar to arms or filopodia.
These structures can help the virus to spread to other cells and promote infection, but further studies are needed to confirm this hypothesis. “The distinct visualisation of the extensive branching of the filopodia once again elucidates how understanding the biology of virus–host interaction can illuminate possible points of intervention in the disease,” said Krogan.