What scientists are learning to try to be ready for what's after COVID-19

CHICAGO – More than a decade ago, a center was founded at Northwestern University as a rapid-response operation against infectious disease. But its work was sporadic — a boom when epidemics hit, a bust when they were under control.

Now, researchers with the Center for Structural Genomics of Infectious Diseases are rushing to find a treatment for COVID-19, making up for lost time. And they hope they'll be ready for whatever comes next.

"I think we're making substantial strides," said Karla Satchell, director of the center who is a professor of microbiology-immunology at Northwestern's Feinberg School of Medicine. "Our hope is that we can do something in time to help this round of the pandemic. But at the very least, we can do enough that this won't happen again."

Andy Mesecar, an expert in biochemistry and gene therapy, is on the front lines of that fight. He has been working seven-day weeks, racing to find a drug for COVID-19, teaching at Purdue University and submitting daily reports to the National Institutes of Health.

His lab is one of the leading centers studying coronaviruses, and he and his team have dedicated nearly two decades to the research. With a background in biochemistry and structural biology, Mesecar started out studying enzymes that could fight cancer. He got into infectious diseases after the anthrax attacks in the weeks after 9/11. Then, he pivoted to studying enzymes that could be used against SARS when it surfaced in November 2002. "My training in structural biology allows me to work on any diseases that go around," he said. "I can apply it to any disease and do so rapidly."

The bulk of coronavirus research began during the SARS epidemic and through the MERS outbreak less than 10 years later. Hardly anything was known about coronaviruses at the time, Satchell said, so researchers sprinted to learn its biochemistry.

During the basic science phase of drug discovery, researchers identify the genetic sequence of a protein or enzyme that is essential to the virus' replication, then look for a compound that blocks it, called the inhibitor. The compounds are developed into a drug that not only lasts long enough in the body to kill the virus but is also nontoxic. Only then can it move to animal trials.

Mesecar spent years studying SARS, then MERS. But as the outbreaks waned, funding dried up. To continue their work, his team scoured for small amounts of funding, but even three years ago, they didn't have enough to support a single person fully. Then the center at Northwestern stepped in.

But the lull in funding had already done its damage, Satchell said. No clinical trials of the compounds had been done by the time the pandemic hit. "Nothing ever got out of the laboratory (for SARS)," she said. "There's no treatment for COVID-19 that is specific to this virus and this infection, and the research tracking it really seems like it just ended."

When MERS emerged in 2012, Mesecar's team switched to this new coronavirus, publishing papers that shared their discovery of compounds that worked against it. He and his team were among the first to predict that the next coronavirus outbreak would come from bats, the suspected origin of COVID-19. "Everything we did was to predict the next outbreak," he said. "What we wanted to do was to have compounds that could rapidly move toward the particular coronavirus strain that emerged."

Satchell, Mesecar and others point to earlier failings as a cautionary tale. Mesecar said researchers should study the effects of certain compounds on animals so they could be more quickly developed when new viruses appear. This was the key to remdesivir reaching patients now. "We're not as far behind as we could be because of the love and ingenuity of scientists who want to pursue and learn about it," he said.

The coronavirus field is undergoing a rapid change. Satchell said, more funding will be needed — and more scientists will need to remain in the field. She's seen this effect with tuberculosis, anthrax attacks and SARS, and she believes this pandemic will yield similar results. In order to be prepared for the next public health threat, she said, scientists will need to break new ground.

"You can make a lot of movement fast, based on what you know," Satchell said. "But at some point, you hit a wall where you have to discover new things."