Decoding Life with MCB: Decoy Proteins

Decoding Life with MCB

Life is extraordinary. So is the work we do. In a brand new podcast, Decoding Life with MCB, the School of Molecular and Cellular Biology at the University of Illinois Urbana-Champaign explores the impact of our students, faculty, staff, and alumni in each episode.

Season 1, Episode 1: Decoy Proteins

Dr. Erik Procko, a professor in the department of biochemistry at the University of Illinois Urbana-Champaign, joins Decoding Life with MCB from Seattle, where he's working to develop and mass produce a COVID-19 therapeutic that will work against variant after variant. Procko takes us back to the early days of the pandemic, when his lab in UIUC's School of Molecular and Cellular Biology shifted gears from studying viruses including Epstein-Barr virus, to SARS-CoV-2.

Transcript

PROCKO: Without doubt, this is the most important research of my career. I'm still on, I'm still on, no off ramp, yet.

LASK: Learn how a University of Illinois professor is doing his part in the fight against COVID 19. You're listening to Decoding Life with MCB. Thanks for listening to Decoding Life. I'm your host, Jen Lask, with the School of Molecular and Cellular Biology at the University of Illinois Urbana-Champaign. We're kicking off season one by sitting down with Dr. Eric Procko, a professor in the department of biochemistry. Procko joins us from Seattle, where his biotech company, Orthogonal Biologics, was acquired back in December by Cyrus Biotechnology. The goal is to develop and mass produce a COVID 19 therapeutic that will work against variant after variant. But before we dive into the science, Procko takes us back to early 2020.

(Overlapping news conference clips) "And to this point, Illinois has successfully contained the virus to two..." "... Currently no cases of COVID 19..." "...and don't get the attitude well, I'm young... "I really want to applaud the private sector for now creating its own...." "The NCAA has shut down all winter and spring sports..." "... and to avoid the loss of potentially tens of thousands of lives, we must enact an immediate stay at home order..." "Those with the head of the state of Illinois..." "... today to report Champaign County's first fatality due to COVID 19 infection...."

PROCKO: You need to keep in mind that when COVID first hit, the beginning was kind of slow motion. I started hearing news out of China and people getting infected on cruise ships. The usual approach in my lab is I often stopped working on new projects, get the assays going, pass them off to students. But then things rapidly escalated. The world's in chaos. The images on the news out of Italy, Iran, China were devastating. All the morgue trucks parked outside the hospitals in New York City and all of the global economies are closed. So at that point, when the shutdowns first came, I made the decision that this was high priority. I was just going to get it done. Literally, the day that the campus closed was the day after my students had their final exam for my part of teaching. So I just finished teaching and I just went full steam ahead into working on it. And then later on, as students came back, they started taking a role, so that that was kind of the beginnings of it.

LASK: The Procko lab had already developed big data tools for deep mutational scanning of transmembrane proteins in mammalian cells. Basically, by combining in vitro evolution with deep sequencing, his lab can then characterize the phenotypes of thousands of receptor mutants in just one experiment. His team can then focus on finding mutations that change protein activity.

PROCKO: We were kind of perfectly situated for when COVID hit. We'd already started working on some viral spike proteins because the very interesting membrane proteins that do not have structural changes.

LASK: Procko's lab was working on Epstein-Barr virus, and interestingly enough...

PROCKO: When we were designing what viruses to work on, we ignored SARS because I felt incorrectly that SARS classical - SARS-CoV-1 - had come, that it had its moment in the spotlight and then it disappeared, petered out. I'd gone to work on other viruses that that seemed more important. So that was a mistake.

LASK: Procko realized early on that his lab would need to pivot.

PROCKO: So in the beginning, I had a friend who was in China. His name's Kui Chan. He's a former graduate student of Illinois. He worked in the lab of Professor John Gerlt, biochemistry, well known by many of the faculty, in fact, in the biochemistry department. And he was running a group in China and we were chatting on the phone and he told me that don't believe anything you're hearing in the news that this is under control. Everyone here is fearful and afraid. The Chinese New Year celebrations were just about to come, and he was off to visit his family in Taiwan, and he decided he didn't want to go back to China. They didn't know what was going to happen."

LASK: Chan came back to the University of Illinois, where he began working with Procko to create a startup company to combat COVID - Orthogonal Biologics. They focused on harnessing their experience in protein engineering to make therapeutics that are safe and effective.

PROCKO: Increasingly, I was getting a sense of panic that I just had to be working on this and solving this problem."

LASK: So, how do decoy proteins play into the fight against COVID 19?

PROCKO: You can take the receptor for the virus, a protein based receptor, which the viral spike binds and uses to attach and infect a cell, and you can make that receptor what we call soluble. So you detach from the host cell and it now is just a protein that floats in solution and it will bind to the virus and the virus is none the wiser. The virus just thinks that this is a receptor, but the receptors not attached to a cell. There's nothing for it to infect. And so it blocks the virus to neutralize very similar to how an antibody works. And so we've been working on those, and the nice benefit of them is that they have the potential to be broad. So, a virus can easily mutate to escape an antibody. We see that now - viruses mutate to escape drugs all the time. But for the virus to mutate, to escape these soluble decoy receptors, usually would mean that then the virus loses the ability to bind its natural receptor on a target's cell, and then the virus becomes what we call attenuated and loses virulence, and it is no longer as dangerous. So the virus is kind of locked in. It can't become resistant. At least it's difficult to become resistant. And with the arrival of Omicron, you have seen all of the monoclonal antibody therapies, which really work very well, and they've all fallen one by one, with the exception of one of them. But it, too, has probably lost some efficacy and potency, whereas we can show that that has not lost any potency. In fact, we are amazingly effective in vitro in a test tube against Omicron. So it's given the program another burst of energy, and we really do feel that we can be relevant so many years into the future, as COVID becomes endemic, against all new variants that arise, rather than the monoclonal antibody approach, which has been very popular because they work. Monoclonal antibodies really work. But it's now clear that that they really are going to have a whack-a-mole approach where every time a new variant comes up, you know, monoclonal becomes ineffective, and now you've got to go out and find a new one and go through clinical trials again. That's far from ideal."

LASK: So far, Procko's proteins have maintain potency against each variant. In late 2021, Cyrus Biotechnology in Seattle announced it had obtained financing and closed on acquisition of the firm. So what comes next?

PROCKO: We're kind of in a bit of a limbo phase where we need to finalize the final drug sequence, drug candidate, to to take it to the FDA to say, "we want to go to clinical trials." That process is very expensive, very expensive, you need to be able to show you can manufacturer a clinical grade material with consistency. So we need to raise the money - millions and millions of dollars to do that. And, you know, to do that, you need to get people interested in what you have and people have always been interested from a scientific perspective. But it's been hard to get enough interest that people will give you at least $5 million to do that preclinical program.

LASK: Procko's not the only one who's been going full steam ahead since COVID 19 emerged. The research here at the University of Illinois has had a ripple effect across the country.

LASK TO PROCKO: Just looking around - We have your research, we have Nicholas Wu's research, we have Pamela Martinez, Chris Brooke working with SHIELD. There's a lot happening around campus that has a ripple effect across the country."

PROCKO: Yes, absolutely. And it has. It has. It's been incredibly important influential research into COVID that has influenced people around the country and around the world, in both a basic understanding, therapeutic development and also for testing capabilities. And Illinois should be proud. It's done a great job with the resources we've had.

LASK TO PROCKO: I just want to kind of look at the bigger picture here. You know, COVID has impacted all of our lives, whether we've had COVID ourselves or know someone that has or as you mentioned, daycares are affected by it. Education. What does it mean to you to be a part of the fight against COVID 19?

PROCKO: I mean, without doubt, this is the most important research of my career. And that is, you know, that as a scientist, you want your work to be impactful and meaningful. You know, we don't just want papers to sit in big, heavy tomes in the library or increasingly just be in the void of ones and zeroes on on the web. We want our work to be impactful. So that's immensely satisfying that you're having a role that can directly improve human society. So, so mostly I'm I'm satisfied that at this point in my career, I feel I am having impact and meaning. And again, that, you know, that inspires one to really try to push through all the way, which in this case means really trying to to reach the clinic to see if we can have impact on real human patients."

LASK: It's been a cross-school, cross-campus effort, with Procko giving shout outs to his lab collaborators, along with Timothy Fan and Diwakar Shukla's Labs in Champaign-Urbana. And Asrar Malik, Jalees Rehman and Lucy Zhang at UIC.

PROCKO: It's been nonstop, and then Omicron hits, and suddenly it's like we we needed the data for how well we work against Omicron yesterday. Not today. Everything's always - you want to have done yesterday, not today. So it's still nonstop. And you know, we're still doing that final burst to finalize our sequence so we can, you know, we can then really say we're ready to begin manufacture. I'm still on, I'm still on. No off ramp yet.

LASK TO PROCKO: A lot of coffee, I'm guessing, in Seattle.

PROCKO: Well, my my caffeine consumption certainly has increased over the past two years. Let's put it at that. Absolutely.

LASK: While Procko is in Seattle for now on leave from the university, his lab at the U of I is still running, and his efforts to help train the next generation of scientists are still ongoing.

LASK TO PROCKO: What is your advice to young scientists and trainees?

PROCKO: Oh. That's that's an interesting question. What would I have done differently? I think I needed to work out sooner what my - to use the same term - criteria of success should be. And I needed to work out sooner that I needed to have a more, you know, on a personal level, satisfaction with with the contributions I was making that weren't simply based on the journal the work was being published in and, you know, citations and things like that. But I really needed my own sense of value for what I was doing. And that took me a while to find.

LASK TO PROCKO: Do you feel personal satisfaction now looking at the research and the role it's playing in the pandemic?

PROCKO: Yes. Yes, I am without doubt doing the most impactful research of my career. Yes.

LASK: We want to give Dr. Procko a huge shout out for taking a break to talk with us for Decoding Life with MCB's first episode. We're excited to share the impact of our students, faculty, staff, and alumni over the course of our first season. After all, life is extraordinary. So is the work we do.

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March 07, 2022 All News