Almost a week after the new coronavirus shut down the University of Colorado medical campus and booted Jed Lampe from his lab, he got the call he had been waiting for Thursday afternoon.
Lampe and two of his fellow researchers received special permission from their department chair and the dean of the Skaggs School of Pharmacy to get back to work on what feels like perhaps the most important and exciting research of their lives: finding a drug that could save people with COVID-19.
The team on the CU Anschutz Medical Campus is one of several at universities and hospitals throughout the world racing to become the first to develop a treatment for the virus, which has killed four people in Colorado and thousands worldwide.
“It’s a race. It’s totally a race,” said Lampe, whose previous research has focused on HIV therapies and drug metabolism. “Competition is a good thing. We push each other along.”
And the work is important not just for now, but for other global pandemics that are certain to follow in the years and decades to come. The intensity of the research surrounding the new coronavirus means that in future years, scientists will have a library of possible antiviral compounds that they could plug in to treat new mutations of viruses — and produce them in real time.
“Hopefully in the future it will allow us to produce drugs faster than we ever have before,” Lampe said. “Next year, we could have a coronavirus that has mutated and is more virulent. How will we handle that? We are really trying to create a game changer here.”
As the new coronavirus began to spread, Lampe joined forces with two fellow CU pharmacy school Ph.D.s whose backgrounds complement his own. Shaodong Dai is an expert in immunology and structural biology. Philip Reigan is an expert in synthetic drug design and is using computer software to model different versions of the compounds before they are tried in Lampe’s lab.
In January, Chinese researchers mapped the entire genome sequence of the new coronavirus and shared it with scientists worldwide. The trio at the pharmacy school in Aurora downloaded the sequence, then isolated a specific part of that sequence — a protein enzyme called a protease, which the virus uses to replicate itself — and ordered a copy of that gene from an international biotech company called GenScript.
In the Colorado lab, the scientists made clones of the protease by inserting the gene into E. coli bacteria, and then began tweaking two HIV drugs — Ritonavir and Lopinavir — to find a version that would fight the virus. The HIV drugs work by attaching to the protease of the virus that causes AIDS, in effect, stopping it in its tracks.
The process of Lampe’s quest goes like this: computer modeling to see which compound will bind with the protease and stop the virus from replicating, then back to the lab, then back to the computer, and so on. Lampe describes the work of figuring out which compound will bind with the protease like finding a missing puzzle piece. He adds atoms to the piece that doesn’t fit, reshaping it, until it does.
The whole point is to inhibit the protease. “Then the virus can’t replicate itself,” he said. “That’s the No. 1 goal of any virus, to replicate, replicate, replicate.”
The CU scientists have done all of this in three weeks.
Even just a few years ago, none of this would have happened so quickly, including the identification of the entire genome sequence within a matter of weeks. “This science is moving so fast now,” Lampe said. “It’s super exciting to me.”
Still, even though the development of an antiviral drug is likely to come sooner than a vaccine, it could take at least a year, he said. The drugs would diminish the symptoms and mean a faster recovery for people who are already sick, similar to the way patients with influenza A or B are helped by Tamiflu.
If the CU team finds a drug that works in their lab, they would next test it on cultures of the virus with the help of a colleague at the Centers for Disease Control and Prevention, Lampe said. Then they would try it on animals, and finally, people who are sick with the new coronavirus.
The federal government could help speed up the process. Lampe was thrilled by President Donald Trump’s announcement Thursday that he would “eliminate outdated rules and bureaucracy” so that work to create antivirals could proceed swiftly.
A study of COVID-19 patients in China that used the same two HIV drugs that Lampe’s team is using for its research had lackluster results, according to a paper published Wednesday in the New England Journal of Medicine. The Chinese researchers gave Ritonavir and Lopinavir to half of 199 patients involved in their study, while the other half did not get them. All of the patients were hospitalized in Wuhan, China, where the outbreak of the new coronavirus began.
“No benefit was observed,” the researchers wrote.
Lampe said it wasn’t too surprising that the drugs did not work well because they are designed to inhibit HIV, not the new coronavirus. This is why he is hoping to modify those drugs to treat COVID-19.
He and his fellow researchers are heading back to the lab Friday morning, three of the few people on campus. “It’s hard for people to have a loved one in the ICU right now, and they want to see a therapy today,” he said. “I get that.”