It’s one of the tiniest machines on the planet — about a hundred times smaller than the average cell. It’s so small that no scientist can spot it through a typical light microscope. Only with an electron microscope can we see its spiky surface. It’s not alive, and it’s not what most of us would think of as “dead.” This teensy machine seems to survive in a kind of purgatory state, yet it has traveled across continents and oceans from host to host, and brought hundreds of nations to a standstill.
Despite its diminutive size, the novel coronavirus, dubbed SARS-CoV-2, has seemingly taken the world by surprise with its virulence. However, it’s not a surprise to cell biologist Carolyn Machamer, who has studied viruses for the past 45 years.
“The beauty of research is that it teaches us things we never set out to learn,” said Machamer in a Pew Charitable Trusts article in 2013.
Machamer has seen the ebb and flow of funding for coronavirus research after other epidemics over the past 20 years, including SARS and MERS, two viruses closely related to the new coronavirus. Although these epidemic outbreaks cause tremendous fear and economic damage in addition to loss of life, few federal research funds have been dedicated to understanding the basic biology of coronaviruses, says Machamer.
“We need to know more about how these viruses work,” she says. “The knowledge can reveal hidden targets and an Achilles’ heel that could help us develop diagnostics and treatments to eradicate them quickly and efficiently.”
A plentiful array of viruses surrounds us. In the ocean alone, Machamer says there are an “astounding number” of bacterial viruses. In humans, scientists have identified several hundred species of viruses, not counting different strains, and it’s likely that number is just the tip of the iceberg.
Viruses are categorized by what their genome is made up of — either DNA or its closely related cousin, RNA. Their genome can be linear or circular, and some have fatty or “lipid” envelopes that surround and protect their genetic material.
SARS-CoV-2 is considered a medium size virus. It’s about 1/100th the size of an average cell. Coronaviruses use so-called fusion proteins that stud their surface — which give them their crowning name — to lock on to a host cell’s outer membrane.
This is not the first time humans have come across coronaviruses. While about 80% of common colds are caused by rhinoviruses and adenoviruses, the remainder are the result of coronaviruses.
There are many strains of coronaviruses, and the SARS-CoV-2 one is completely new to humans. There are more than 100 strains of rhinoviruses, and that’s why people get lots of colds, says Machamer.
Coronaviruses also infect birds, and Machamer studies an avian model of the virus in her laboratory at the Johns Hopkins University School of Medicine. Her focus of research is on the unusual way coronaviruses assemble their progeny within a host cell.
First, the virus enters an animal’s body through a mucus-lined surface — the nose, mouth or eyes. It uses its crown of proteins to fuse to a host cell surface or a cellular package called an endosome, which is engulfed by cells.
Once inside the host cell, the virus uses the first two-thirds of its genome to replicate. It copies its genome and makes structural proteins critical to form new viruses that will soon escape the host cell. But instead of going straight to the cell membrane to get ready to be shipped out of the host cell, the virus stops at a pancakelike structure called the Golgi complex, a kind of post office for the cell that sorts and processes proteins and spits them out of the cell after enclosing the proteins in a compartment called a vesicle.
At the Golgi complex, coronaviruses assemble new viruses and package them, using a piece of the Golgi complex’s membrane to form the new virus’s lipid envelope. Then, the Golgi complex stuffs the newly formed viruses into vesicles, which make their way to the cell surface.
“It’s not the most efficient way to assemble viruses and get them out of a cell,” says Machamer. “But there has to be a reason why this mechanism has persisted.”
Other viruses also use the Golgi complex to assemble their offspring. The most well known one is rubella (German measles).
Other viruses, such as West Nile, hepatitis C and Zika, use a different cellular structure to assemble new viruses: endoplasmic reticulum, which is made of membranes that foster protein production in the cell.
Machamer recently found that coronaviruses neutralize the pH of the Golgi complex, potentially paving a better path to help the germs, with their spiky halo, escape cells.
She says there has been a flurry of new scientific information about SARS-CoV-2 that needs to be further evaluated.
There is some evidence, she says, that SARS-CoV-2 has picked up mutations in its spiky crown of proteins that help the virus bind more tightly to cells. “This could be one reason why SARS-CoV-2 is more infectious than other viruses,” says Machamer.
Scientists will need more investments in research to face such global threats, and Machamer says it’s shortsighted to focus most of those resources on vaccines and therapies. “We need to understand how these viruses work,” she says, “and once we understand that, we’re in a better position to conquer them.”
For information from Johns Hopkins Medicine about the coronavirus pandemic, visit the coronavirus information page. For information on the coronavirus from throughout the Johns Hopkins enterprise, including the Johns Hopkins Bloomberg School of Public Health and The Johns Hopkins University, visit the coronavirus resource center.