Inside his laboratory at Washington State University, Michael Letko is determined to give the world a leg up on the next pandemic.
Letko, a new assistant professor in the Paul G. Allen School for Global Animal Health, is working on expanding the ever-growing database of the world’s coronaviruses with new data he is acquiring through some unique experimental approaches developed in his lab.
Earlier in January, he published his findings from the past two years on all known variants of one entire sub-branch of the coronavirus family tree, which includes SARS-CoV-1 and SARS-CoV-2.
Letko studies the coronaviruses the world doesn’t know about yet – and there is plenty to study.
“There are likely thousands of coronaviruses out there circulating in nature. If an animal is warm-blooded, it probably has a coronavirus, at least one,” Letko said. “I want to get a better idea in the lab for which of those coronaviruses have the potential to infect human cells.”
Eventually, he wants to develop a database that can help assess the potential for novel animal viruses to be transmitted to humans. New viruses would automatically be ranked based off of similarity to known viruses and how those viruses performed in his lab’s various experiments. Thus with a new sequence, scientists would be able to better predict crucial information, based off an expansive database of laboratory-acquired data.
While this vision is still a bit far off from now, coronaviruses are a great starting point for this work, Letko says, given their ubiquity and ability to sometimes jump between species.
How he does it
The work is all made possible by synthesizing the small fragment of the virus that is responsible for allowing the virus to infect cells. Letko then uses various molecular biology techniques to test these small fragments for their ability to interact with human cells. When he finds a match, the cells glow bright green, indicating his fragments have made their way into the cells.
This process is cheaper and faster than previous methods, allowing him to test several viruses all at once. Importantly, his work does not require a whole virus, so Letko is able to safely test small pieces of viruses without risk of accidental infection.
In January, he became one of the first scientists in the world to test cell entry of SARS-CoV-2, the causative agent for COVID-19, and determined the virus was targeting the ACE2 receptor.
That same receptor was targeted by SARS-CoV-1, discovered in 2003.
“Immediately we knew the virus was likely to infect certain cells in the lungs, which gave clues into the transmission rate data that was beginning to emerge at the time,” Letko said. “It was this early glimpse into what we were working with that made it apparent from the beginning SARS-CoV-2 was like SARS-CoV-1 and could be quite severe.”
A head start for humanity
The goal of his research at WSU is to help give the world a head start on the next pandemic, and ultimately, save time and lives.
That’s why he is going after the backlog of coronaviruses that have been sequenced and have since mostly just collected dust.
There are thousands of examples, many coming from the world’s more than 1,400 species of bats.
Letko looks to answer a few questions about each one.
“What kind of cell does it infect? What types of receptors does it use?” Letko said. “If you know those basic things you can get an idea of what coronaviruses can be passed from animals to humans and even how a vaccine might work.”
Letko’s always been fascinated by the viral host but he didn’t start his career examining coronaviruses.
Before coming to WSU this month, Letko worked for four years at Rocky Mountain Labs in Hamilton, Mont., studying emerging viruses such as MERS-CoV, SARS-CoV, Nipah, and Ebola.
He received his PhD from Icahn School of Medicine at Mount Sinai in New York City. He looked at the coevolution of HIV, in humans and primates and how viruses subvert their host’s defenses.
“I was eager to apply what I learned with HIV to some of the more contemporary emerging pathogens, like filoviruses, coronaviruses and Nipah virus,” Letko said.
In the middle of a COVID-19 world pandemic that has killed nearly 650,000 people, he knows he made the right move.
“We all say that the emergence of a new virus was expected and bound to happen, but this is still shocking – even in the scientific community,” Letko said. “These cross-species spillover events probably happen probably more often than we appreciate, and they are likely to keep happening. It’s time we try to get out in front of them.”