Coronavirus Hijacks Cells Forces Them To Grow Tentacles Then Invades Others

August 19, 2020

According to a new study, cells infected with the new coronavirus grow tentacle-like chord-like arms that allow the virus to invade other cells.

The new coronavirus, known as SARS-CoV-2, has infected more than 12.2 million people worldwide and killed more than 555,500 people, according to a dashboard from Johns Hopkins University. To defeat this virus, researchers around the world are taking part in an unprecedented effort to find new drugs and repurpose old ones.

But to truly find the right weapon for treatment, scientists need a detailed understanding of how the virus invades human cells. To get to the bottom of this, an international team of researchers studied how viruses alter the activity inside cells in order to invade more and more cells. In particular, they analyzed how viruses alter certain proteins in infected cells. (Proteins carry out genetic instructions, so changes in proteins may affect the actual actions of infected cells.)

The new study builds on a “blueprint” of 332 human proteins that interact with 27 SARS-CoV-2 viral proteins described by the researchers in April in the journal Nature. In the new study, the researchers analyzed all the human proteins that, according to a statement, changed after infection in a process called phosphorylation – in which a protein called a kinase sticks a phosphate group (a phosphorus atom attached to three oxygen atoms) to other proteins.

Phosphorylation is a process that activates and deactivates proteins and is “extremely important” for many cellular processes, including protein synthesis, cell division, signaling, cell growth, development and aging, according to an article published in the International Journal of Molecular Medicine in June 2017.

This group of kinases is like a “master switch for the cell,” said senior author Nevan Krogan, director of the Quantitative Biosciences Institute (QBI) at the UCSF School of Pharmacy and a senior researcher at the Gladstone Institute.” If a virus can come in and manipulate the switchboard, it can manipulate things in a way that favors infection.”

Using a method called mass spectrometry to measure the mass of different molecules, such as proteins, the team found “dramatic rewiring of phosphorylation on host and viral proteins” in monkey cells, the authors wrote in their new study.Krogan told Live Science that the method can identify subtle mass changes between phosphorylated and non-phosphorylated proteins.

Tiny cells
The proteins in human cells are very similar to those in monkey cells, Krogan said. The team found that 40 of the 332 human proteins previously found to interact with coronavirus were phosphorylated differently in virus-infected monkey cells compared to uninfected cells.

In addition, of the 518 kinases they examined, the scientists found changes in the phosphorylation activity of 49 of them, according to the statement. A couple of the kinases, including the so-called casein kinase II (CK2), had their activity dramatically altered by the virus and were located within important cell signaling pathways, according to the statement.

High-resolution imaging of the infected cells showed that the cells grew tentacle-like protrusions called “filopodia,” which contain viral proteins, according to the statement. The researchers found CK2 and viral proteins within the filopodia, suggesting that the coronavirus hijacks CK2 and forces it to form tentacles. These tentacles then make holes in nearby cells, allowing the virus to infect new cells, according to the statement.

The researchers then identified 87 drugs, either approved by the U.S. Food and Drug Administration (FDA) or currently in clinical trials, that may target some of these kinases or pathways that were altered by SARS-CoV-2 in human and monkey cells. The kinases are “very druggable,” Krogan said.Krogan said they found that seven of these compounds, primarily anti-cancer and anti-inflammatory compounds, inhibit the replication and growth of the virus in human lung cells and monkey kidney cells.

The study “is careful and thorough, but has some limitations,” said Carol Shoshkes Reiss, a professor of biology and neuroscience at New York University.” He was not involved in the study. The researchers used non-human cells, rather than primary human airway cells, to test how the virus infects the cells, she said. The authors acknowledged this limitation of the study, she added. They also did not demonstrate that their ideas work in any of the top animal models used to study SARS-CoV-2 infection, such as transgenic mice or hamsters, she told Live Science in an email.

“It definitely has potential if it’s properly tested,” she said.” However, you have to be aware that these pathways are essential, and while there are licensed drugs for them, the potential for side effects and off-target effects is high.”

The results of the study were published June 28 in the journal Cell. The Krogan lab was supported by research from Vir Biotech and F. Hoffmann-La Roche, and one of the co-authors has consulting agreements with several pharmaceutical companies.