Most of us have already absorbed the idea that the coronavirus does some strange and sinister things to the human body that are different from most other respiratory viruses known to man. But now a new study finds another disturbing thing that the virus appears to be doing to help spread from one cell to another.
A new study by an international team led by UC San Francisco finds that cells infected with SARS-CoV-2 quickly begin to develop new arms or dendrites, clinically referred to as filopodia, that are studded with fresh virus particles. These filopodia seek to reach and pass through the walls of neighboring cells, thus infecting. And this appears to be a second way for the virus to replicate and spread in the body.
As the LA Times reports through the study, until now, researchers believed that this virus spread like most other viruses, by attaching itself to healthy cells, invading and then turning those cells into copy machines. A team at the UCSF Institute for Quantitative Biosciences led by systems biologist Nevan Krogan launched a project in February to quickly identify existing drugs and compounds that could treat or delay the spread of the coronavirus. They published initial findings in late April that pointed to 10 existing drugs and experimental compounds that showed promise in laboratory settings when it came to attacking the human proteins this virus needs most to survive.
The latest study is an extension of that work, and Krogan is one of the lead authors of the article published today in the journal Nature. The major new finding, Krogan and the team hope, will lead to a quick study of several existing cancer treatments that inhibit the growth of phyllopedia, so shutting down this second means the virus is using it to invade cells.
“It is so sinister that the virus uses other mechanisms to infect other cells before killing them,” says Krogan, speaking to the LA Times.
Krogan says that while other viruses, including HIV and the family of viruses that cause smallpox, also use philopaedia as mechanisms for spreading infection, the way this virus causes these tentacles to grow is very unusual. And their shape, branching out of the cell and into each other like trees, is also apparently strange. Other infectious diseases like HIV do not cause this type of prolific and mutant growth.
Expanding on the above list of promising drugs, the latest study points to seven cancer drugs that are already in use and that could be effective against COVID-19. Those include a medicine already used to treat acute myeloid leukemia called Xospata (generic name: gilteritinib); the experimental drug Silmitasertib, which is being studied as a treatment for bile duct cancer and a form of childhood brain cancer; and ralimetinib, another anticancer drug developed by Eli Lilly to treat multiple forms of cancer.
All of these medications are known as kinase inhibitors, which is also the treatment of Gilead remdesivir.
“We have tested several of these kinase inhibitors and some are better than remdesivir,” says Krogan, through the Milwaukee Journal-Sentinel.
The research team found that another experimental drug called Dinaciclib stops the virus from attacking a family of kinases called CDKs, which are responsible for cell growth and DNA damage.
Other infectious disease researchers are just picking up on the revelations in the article, but most of the reactions seem quite excited. While much research is being done on the shutdown of virus proteins, Krogan’s field of study, called proteomics, focuses on the least likely human proteins to mutate involved in helping the virus do its dirty work.
“This article shows how completely the virus is able to reconnect all the signals that pass within the cell,” Andrew Mehle, professor of medicine at the University of Wisconsin-Madison, tells the Journal-Sentinel. “That is really remarkable and it is something that happens very quickly (as soon as two hours after the cells are infected).”
And Lynne Cassimeris, a professor of biological sciences at Lehigh University, calls the latest findings “a surprising leap.” “We know that the virus has to manipulate these human proteins,” says Cassimeris. “We now have a list of what is changing over time.”
While Krogan’s lab at UCSF took off this research just as the pandemic erupted in February, there were 70 authors in the last article, with Krogan leading. The work was also carried out by scientists in the bush. Sinai Hospital in New York, Rocky Mountain Labs in Montana, the Pasteur Institute in Paris and the University of Freiburg in Germany
