Scientists find the Achilles heel of the coronavirus

The coronavirus pandemic has spread worldwide, infecting more than 10 million people. As it continues to wreak havoc, many scientists are working to determine a potential weakness in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to find an effective drug or vaccine against it.

A team of scientists from the University of California at San Francisco discovered how SARS-CoV-2, the virus that causes coronavirus disease (COVID-19), invades proteins in cells that serve as master regulators of cellular processes. key. The virus can rewire cell circuits to promote their survival and proliferation. Scientists also suggest that attacking the pathogen’s dependence on host cell proteins could be the heel or Achilles weakness.

The study, published in the journal. Cell, highlights the possibility of attacking the weakness of the virus so that it can be eliminated, potentially stopping the global pandemic.

The coronavirus forces cells to produce tentacle-like structures that infect neighboring cells.

How does SARS-CoV-2 infect cells?

SARS-CoV-2 is a rapidly spreading virus that has devastated the world, killing more than 515,000 people. A key to stopping the spread of the virus is understanding how it enters cells.

SARS-CoV-2 uses the human angiotensin converting enzyme 2 (ACE2) as an input receptor to gain access to cells. The virus’s peak proteins 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.

From there, the virus hijacks the cell’s protein-making machinery to translate its RNA into new copies of the virus. In a few hours, a single cell can produce many new virions, which 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.

They also discovered that when SARS-CoV-2 infects cells, it has control over a group of enzymes called kinases. Kinases generally 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 fixation, 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 can behave differently, which can alter cellular function and transform the host cell into a virus factory. These possessed cells then develop flux filaments, or filopodia, which are tentacle-shaped structures that pierce the cells ‘bodies and inject their viral venom into the cells’ genetic command centers, creating another virus factory.

The researchers noted that these new dendrites strengthen the efficiency of SARS-CoV-2 to capture new cells and establish infections in humans.

Although other viruses, including Marburg, Ebola, and vaccinia, are known to create filopodia, this is the first time they have been observed in coronaviruses. Scientists also believe that the new coronavirus can use filipodia as an infectious transport system.

Potential drugs

Scientists also believe they have identified several medications that could help alter the viral absorption of cells. These medications may have the potential to treat patients infected with the coronavirus.

“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 possesses antiviral efficacy, representing potential COVID-19 therapies, “the researchers wrote in the article.

Medications identified include anticancer drugs that work by blocking the chemical signals that activate filipodia production. These include Silmitasertib, an experimental drug for the treatment of bile duct cancer, Ralimetinib, an experimental small-molecule cancer drug in development by Eli Lilly.

“We are encouraged by our findings that drugs targeting differentially phosphorylated proteins inhibited SARS-CoV-2 infection in cell culture.” We hope to build 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, “Dr. Kevan Shokat, professor of cellular and molecular pharmacology at UCSF and lead co-author of the study, he said.