By Randolph Fillmore
The “Swiss army knife” of viruses
On a recent National Public Radio program, Mark Denison, MD, professor of Pathology, Microbiology and Immunology at Vanderbilt University, called the corona virus sweeping the world the “Swiss army knife” of viruses.
He explained that the virus, called SARS-CoV-2, which causes a disease called “COVID-19, is a “jack-of all-trades,” a unique corona virus, highly infectious, able to easily adapt, with a structure that enables it to “pick the lock” of human cells and enter. Once inside the cell, it replicates and causes havoc.
Other corona viruses, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are related corona viruses, but SARS-CoV-2 is unique, said Denison, who has studied a variety of corona viruses for over two decades,
Denison added that virologists knew that something like SARS-CoV-2 would emerge eventually but did not know when. Potentially good news, he said that SARS-CoV-2 is “one type” and that it is not evolving.
Structure and function
The spikey nature of the corona on SARS-CoV-2, looking like a crown, or sharp rays coming from the sun, gives corona viruses their moniker. According to University of Texas-Austin researchers, the “tool” the virus uses to break into cells is a “spike protein” on the cell surface that binds with a receptor protein ACE2 on the surface of respiratory cells. Targeting that interplay between the spike protein and ACE2 “cracks” the cell. Disrupting that interplay might be the key to “cracking the case” of SARS-Cov-2. They published their research in the March 13, 2020 issue of Science Magazine (AAAS).
On his university website, Denison says that corona viruses are a genetically diverse family of viruses that infect birds and mammals, with most strains infecting only certain “hosts.” Human coronaviruses cause up to 30 percent of common colds. When viruses jump between animals and humans, they are referred to as “zoonotic.”
In the last 15 years, explains Denison on his website, coronaviruses have demonstrated an ability to “jump into new species” and cause both SARS and MERS.
Don’t be fooled into thinking that SARS-Cov2 is like the flu. It’s not. Influenza is known to migrate seasonally, but the corona virus called SARS-Cov-2 doesn’t need to do that. Any host, anywhere, will do. And, if it needs to, the virus can adapt. It’s even been called a “proofreader” owing to its ability to adjust and correct its own genetic “mistakes” to survive.
Keep it clean
SARS-Cov2 is 1,000 times better at binding to human proteins than other viruses. However, it desperately needs a host (us) to survive. How can we defeat it? Perhaps by depriving it of hosts is one strategy, through social distancing. Speaking on a March 13 podcast from The Journal of Clinical Oncology, Emily Landon, MD, director of infection and control at the University of Chicago said that the “magic number” for keeping distant from anyone is six feet because that is the distance, under normal conditions, that small droplets can stay in the air. She also said that when cleaning surfaces with wipes it is necessary to observe long contact time, keeping the surfaces as wet as possible for several minutes. If you must fly, she recommended wiping down the airplane arm rest, tray table, and window if you are in a window seat. If you do wear a mask you must leave it on for the whole flight. If virus is on the outside of the mask, you can infect yourself by touching it. So, be careful when removing and discarding it.
Inhibiting its ability to enter cells is yet another strategy, and one being pursued.
Finding a way to keep SARS-Cov-2 from breaking into cells
It is not news that there are no specific therapeutics approved by the U.S. Food and Drug Administration (FDA) to treat people affected by SARS-CoV-2 and who have acquired the disease called “COVID-19. However, hope (springing eternal) may be on the horizon.
A re-purposed experimental drug, GS-5734, also known as “remdesivir,” developed by Gilead Science, Inc. in California, mostly failed in its attempt to rescue people from Ebola a decade ago. The drug did show promise in stopping Ebola in animal models, but “fizzled” in humans, according to a March 11, 2020 article in The Washington Post.
The best hope is that remdesivir will rise Phoenix-like from its Ebola ashes and stop the spikey protein in SARS-CoV-2 from breaking into human cells and binding to proteins in the respiratory system, thus shutting it out and shutting it down.
As you read this, Gilead Sciences says it is working closely with many agencies, including the National Institute of Allergies and Infectious Disease (NIAID/NIH) and using it on a few patients who have contracted COVID19. Two NIH-funded clinical trials are ongoing, one at the University of Nebraska and the other is being conducted in China. Remdesivir has been called “promising.”
“I don’t know whether it is being called promising because the company is talking about it so much, or that it is promising because it is promising,” said Landon in her podcast.
Remdesivir (GS-5734) has been around for quite a while. Denison and his collaborators found years ago that GS-5734 reduced the “viral load” on the lungs of mice and improved their respiratory function.
In the past, Denison and his collaborator for almost 20 years, Dr. Ralph Baric at the University of North Carolina, in the past showed that GS-5734 could inhibit both SARS and MERS in test tube samples of human airway cells.
NIAID director Anthony Fauci, MD and a member of the US Corona Virus Task Force, recently said that remdesivir has been administered to some patients with COVID-19 but that “we do not have solid data to indicate it can improve clinical outcomes.”
In January 2020, Denison, Baric and their collaborators, continuing to test remdesivir in combination with other drugs, reported in Nature Communication that CoVs “…seem to play by their own rules while dancing at the edge of genetic disaster.”
Let us hope that the disaster awaiting SARS-Cov-2 precedes the potential disaster looming over us.