Since the first cases of the new coronavirus, COVID-19, were recorded, scientists around the world have entered a race against time in which they seek to find a ‘Achilles heel’ of the Sars-CoV-2, in order to develop a vaccine that counteracts its serious and deadly symptoms. Those efforts have paid off, US researchers discovered that attacking the pathogen’s dependence on host cell proteins could be the heel or weakness of this pandemic virus.
The research is led and developed by scientists at the University of California, San Francisco. This research team unveiled how COVID-19 could invade cells that serve as master regulators of key cellular processes. In addition, they showed that the virus could rewire cell circuits to promote its survival and proliferation. In this process they found a possible method by which they could attack the virus through immunization and thus be able to stop the pandemic that has claimed hundreds of lives.
How COVID-19 enters the body and infects it
As the medical-scientific literature has already shown, Sars-CoV-2, the virus that causes COVID-19, uses the human angiotensin-converting enzyme 2 (ACE2) as an input receptor to gain access to cells. That is, it is the method with which COVID-19 enters the body and infects cells.
Doctors and healthcare professionals are most concerned about the virus’s proteins that they bind to ACE2, which plays a role in regulating blood pressure. When the virus binds to it, it triggers chemical changes that can fuse the membranes around the cell and the virus. In turn, the RNA from the virus can enter the cell.
According to the study, after this process, the virus hijacks the cell’s protein-producing machinery to translate its RNA into new copies of the virus. In a few hours, a single cell can produce many new virions that can infect other cells in the body.
Key cell input mechanism
The team has identified key mechanisms of SARS-CoV-2 cellular entry that can potentially contribute to immune evasion, cellular infectivity, and the widespread spread of the virus.
Another finding from this research that would open up the spectrum for new therapeutic horizons is that when SARS-CoV-2 infects cells, it has control over a group of enzymes called kinases. In most cases, kinases play a critical role as master regulators of growth, metabolism, repair, movement, and other vital cellular processes.
They attach small chemical labels to proteins through a process known as phosphorylation. After attachment, the tags act as switches that can turn proteins on or off, allowing complex machinery to function properly and smoothly.
However, when SARS-CoV-2 gains control of the cell, the kinases may behave differently, which can alter cellular function and transform the host cell into a virus factory.
The main problem of kinases starts from the previous premise, since once these possessed cells develop flux filaments or filopodia – tentacle-like structures that pierce the cells ‘bodies and inject their viral venom into the cells’ genetic command centers – creating significant virus production.
Pharmacological treatment: effective against cellular viral absorption
“Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to kinases and deregulated pathways. We found that pharmacological inhibition of p38, CK2, CDK, AXL and PIKFYVE kinases has antiviral efficacy, representing potential COVID-19 therapies, ”the researchers wrote in the article published in the journal Cell.
Some of the candidate drugs for virus treatment are used for cancer because they work by blocking the chemical signals that activate filopodia production. These are:
- Silmitasertib: an experimental drug for the treatment of cancer of the bile ducts.
- Ralimetinib: An Experimental Small Molecule Cancer Drug Developed by Eli Lilly.
“We are encouraged by our findings that drugs targeting differentially phosphorylated proteins inhibited SARS-CoV-2 infection in cell culture. We look forward to building on this work by testing many other kinase inhibitors while simultaneously conducting experiments with other technologies to identify underlying pathways and additional potential therapies that can effectively intervene in COVID-19, ”said Dr. Kevan Shokat, professor of pharmacology. Cellular and molecular at UCSF and co-author of the study.