Preparing for Tomorrow’s Pandemics, Today
by Amanda Rossillo | American Scientist Magazine | June 25, 2021
Named one of American Scientist’s top 3 blog posts of 2021
Close up of SARS-CoV-2, the virus that causes COVID-19. Courtesy of Fusion Medical Animation on Unsplash.
Invisible viruses are circulating all around us. Although many do not infect humans, some have the potential to spill over into our species. These viruses, known as emerging viruses, are found all over the world, and include coronaviruses such as SARS-CoV-2, which causes COVID-19. However, experts warn that SARS-CoV-2 won’t be the last coronavirus to make the jump to humans, and that we need to be prepared to treat new emerging viral infections before they begin infecting humans.
On April 27, Sigma Xi, The Scientific Research Honor Society, hosted a virtual presentation with Timothy Sheahan, a virologist at the University of North Carolina at Chapel Hill Gillings School of Global Public Health, as part of its Pizza Lunch series. Sheahan discussed his research on developing broad-spectrum antiviral medications to treat infections caused by emerging viruses. He focuses on coronaviruses, which have crossed the species barrier from bats to humans three times in the last 20 years (in 2017, we first covered Sheahan's work in Progress Against Viruses in Animal Reservoirs).
Although human coronaviruses were first recognized in the 1960s, this group of viruses was not known to cause serious disease before the emergence of SARS-CoV in 2002, which causes Severe Acute Respiratory Syndrome (SARS). Ten years later, MERS-CoV, which causes Middle East Respiratory Syndrome (MERS), emerged. Neither became a pandemic, but MERS is fatal in 35 percent of cases.
Recognizing the urgent need for coronavirus treatments, in 2015 Sheahan began working on developing a single, broad-spectrum drug that could treat multiple distinct coronaviruses, including those that haven’t yet spilled over into humans. Coronaviruses’ genetic material is encoded in RNA—a molecule similar to DNA—which consists of building blocks that are assembled in a chain. Sheahan’s work involves disrupting the chain by adding structurally similar yet nonfunctional blocks, preventing the virus from copying its RNA and reproducing in its hosts. This class of antiviral, known as a nucleoside analog, is most effective in the early stages of infection.
Remdesivir, a nucleoside analog antiviral that was the first FDA-approved coronavirus treatment, was originally developed to treat the RNA-based Ebola virus in 2015. However, Sheahan and colleagues found that remdesivir is also effective at disrupting the reproduction of multiple coronaviruses in laboratory settings.
“A lot of your symptoms are driven by your body’s reaction to the virus replication. So depending on where you are in your time after infection, a drug like remdesivir will work best at the beginning when the virus is actually doing its replication,” Sheahan said during the Q&A portion of his talk.
Because remdesivir had already been shown to be safe in humans several years prior, it was fast-tracked to clinical trials for COVID-19 and was approved for emergency use in May 2020. Full FDA approval was granted in October 2020. Typically, however, advancing from preclinical laboratory testing to clinical trials and FDA approval takes at least a decade.
Sheahan explained that part of the process of developing an effective antiviral is ensuring that it will still work at doses that are safe. “In cells in a dish, you can pretty much make anything look antiviral,” Sheahan said during the Q&A. “But the important thing to note is, how much do you have to give your cell culture to make that happen? And can you give a person an equivalent amount of that drug without killing them?”
Currently, remdesivir is only available via an injection administered in a hospital setting. For the past several years, Sheahan and his colleagues have been developing a new oral nucleoside analog known as molnupiravir that, if authorized for emergency use or approved by the FDA, could be taken at home. The drug is currently in the final phase of clinical trials and could be submitted for emergency use authorization before the end of 2021.
However, Sheahan stresses that therapeutic treatments such as remdesivir and molnupiravir are not replacements for vaccines. “Vaccinations are definitely the best tool that we have,” he said during the Q&A.
What can public health systems do to prepare for future spillover events? Sheahan advocates for a One Health approach, which recognizes that the health of humans, animals, plants, and our shared environment are intricately linked. By investigating existing viruses within other species such as bats, scientists can anticipate which have emergence potential and can develop vaccines and therapies before they’re needed.
Still, misinformation about SARS-CoV-2 and COVID-19 abounds, and it can be challenging to understand the nuances of biomedical research. If you have the background or knowledge, Sheahan says that having conversations about vaccines and viruses with your friends and loved ones can help:“Informed citizens can do a lot.”