Things change fast. Even just a few months ago, most of us who aren’t virologists, microbiologists, or veterinarians, had probably never heard of coronaviruses. Yet last week, the Centers for Disease Control and Prevention advised that it’s not a question of whether the outbreak of a coronavirus known as SARS-CoV-2 (and its associated disease, COVID-19) would spread in U.S. communities, but when — and we should be prepared for potential disruptions in our daily lives as a result. The number of confirmed cases in the U.S. has been rising steadily in the last few days.
But this change didn’t come out of nowhere. Even though this particular viral strain only recently emerged as a new human disease, coronaviruses have been around for a very long time. Likewise, Susan Weiss, PhD, a professor of Microbiology at the Perelman School of Medicine, is newly quite busy launching research projects to help respond to the threat of the novel coronavirus — but coronaviruses generally have been a major focus of her research for four decades.
Before 2003, there were only two known coronaviruses that infect humans, both of which are causes of the common cold, but not fatal disease. Weiss noted that the earliest-known coronaviruses also included several viruses that caused disease in other animals including pigs, cows, cats, and birds, so scientists have focused on developing vaccines for those diseases over many years. And quite a lot of research, including Weiss’s own since 1980, has focused on murine (mouse) coronaviruses. It’s thanks to mice — and the usefulness as a model to help find treatments for various diseases — that we know a fair amount about the underlying biology of coronaviruses today. Since 1949, when murine coronavirus (also called mouse hepatitis virus) was first isolated, scientists have studied it in the lab, particularly some of its common strains that infect the liver and brain. Weiss’s lab uses the mouse coronavirus to study the underlying genetic and molecular mechanisms of how infection leads to illness in diseases including acute viral encephalitis, multiple sclerosis, and virus-induced hepatitis.
Coronaviruses first became better known among non-scientists in early 2003 thanks to the virus family’s first famous human disease: Severe Acute Respiratory Syndrome (SARS). The agent, called SARS-CoV, started to cause illness in southern China before spreading to North America, South America, Europe, and Asia. “It was really scary because there was a high mortality rate, but compared to what’s going on now, it was fairly contained and small,” Weiss said. Ultimately SARS dissipated within about eight months. Since 2004 there have been no more known cases. But SARS was a warning shot — more viruses like it could be out there, on the verge of transforming into strains that cause serious human illness. Based on analyses of the SARS virus and searches for related genetic sequences in the environment where it emerged, scientists determined that the human virus evolved from a bat coronavirus that infected a civet, from which it mutated again and jumped to humans.
“After SARS, people started looking for human coronaviruses, and two others were identified,” Weiss said. These new strains caused some more severe symptoms than a typical cold but were still rarely fatal.
Nearly a decade after SARS, MERS, or Middle East Respiratory coronavirus (MERS-CoV), began causing illness primarily in the Arabian Peninsula in 2012, and was later found to have evolved from another bat coronavirus that had infected dromedary camels. MERS had an even higher fatality rate than SARS but it didn’t spread as far. Camels remain a reservoir of the disease to this day and new human infections continue to be detected.
Now that the novel coronavirus (SARS-CoV-2) is sweeping the globe, the scientific community is springing into action to understand and fight it. Weiss’s lab, which already had been at work on MERS-CoV for over five years, is now beginning studies of the human antiviral immune response to SARS-CoV-2, as well as partnering with collaborators at Colorado State University to study the mechanisms of infection and immune responses in live bats and bat cells.
As a longtime epicenter of coronavirus research, Weiss’s lab has also helped to train scientists now working jumping into the fray all over the world. Alumni from her lab are at work on the development of vaccines, public health preparedness, and additional scientific studies of the virus to make it possible to manipulate the viral genome.
Even if this coronavirus outbreak seems sudden to most of us, for Weiss, it’s an object lesson in why the slow and steady work of scientific discovery really matters, including on niche topics: “The many years of research by the early group of coronavirologists on mouse hepatitis virus and veterinary pathogens taught us an enormous amount about the coronaviruses and prepared us for understanding these lethal human pathogens that would emerge from zoonotic hosts,” she said. As a result of that previous knowledge, she said, the cause of SARS was quickly identified and genetically sequenced soon after people became sick, and it happened even faster yet with MERS-CoV and SARS-CoV-2. “It is gratifying to see how those years of research and mentoring can aid during health crises. One lesson to be learned is that it is crucial to support basic research that may not seem to have immediate impact on human health.”