As the world continues to battle the novel coronavirus known as COVID-19, we've all become accustomed to images of physicians, biologists and chemists draped in hazmat suits and personal protective equipment, working tirelessly in laboratories searching for treatments and vaccines — the place we assume the breakthroughs will be found.
Well, it turns out that important discoveries are also being made through computational studies in computer labs all around the globe.
And in the Blugold chemistry lab, using the Supercomputing Cluster at the University of Wisconsin-Eau Claire.
Two Blugold chemistry faculty, Dr. Sudeep Bhattacharyay and Dr. Sanchita Hati, have recently published a peer-reviewed research article in the ACS Omega, a peer-reviewed journal published by the American Chemical Society, which has made important conclusions about the way the proteins of the SARS-CoV-2 virus (COVID-19) interact with human cells — findings that could provide insight into possibilities of mitigating the severity of symptoms through changes in certain behaviors.
The article, titled "Impact of Thiol–Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin-Converting Enzyme 2 Receptor," is the basis of continued research now taking place with the help of nine student researchers.
"It all started during the spring online session when we were confined at home, and were curious about this new coronavirus disease, and why certain underlying conditions made patient outcomes so much more severe," Bhattacharyay says. "Because we had seen research showing that oxidative stress had implications in the outcomes of the influenza virus and HIV infections, we decided to explore the COVID-19 infection and its severity under oxidative stress."
Hati describes oxidative stress as "an imbalance in our cells of free radicals versus antioxidants — free radicals being very reactive are dangerous to our cells, and antioxidants beings agents that eliminate free radicals from our bodies.
"To understand the molecular basis for the variations in the severity of the COVID-19 infection, we examined the effect of redox changes on the binding of the viral spike protein to our cell surface receptor using computational tools."
Research method — ideal for several reasons
Using the Blugold Supercomputing Cluster, the Hati-Bhattacharyay study employs robust computer models to simulate biochemical reactions between the virus and human cells, a computational research process explained further by student researcher Carl Fossum. Fossum is one of nine students in the Hati-Bhattacharyay lab at this time who are furthering the research begun in the recent published study.
"Computational chemistry is an incredibly interesting and important field in science that combines physics, chemistry, biology and computer science," says Fossum, a junior chemistry and physics major from Eau Claire. "In today's world, nearly every research project that involves materials on the nano level begins with a computational scientist. Computers allow us to simulate ideal laboratory environments to quickly get theoretical data without the time and expense of laboratory experimentation."
With regard to COVID-19 and the urgent need for a vaccine, Fossum points out that the scientific community has spent a great deal of effort computer-simulating the virus’s interactions within the body and collecting data that has been freely shared around the world. Individual labs are now working on vaccines based on these computational theories.
Fellow student researcher Jessica Liebau explains how traditional lab studies and computational studies work together.
"Many times, computational work and experimental work are complementary; the computations explain why, and the experimental results help us to ground the project with real experimental values and prove if the computational methods and findings are correct," says Liebau, a senior from Madison double-majoring in biochemistry/molecular biology and Spanish.
The published findings — and what they mean
So what does this discovery mean for those of us left a bit "in the dark" by the complexity of the chemical terminology? It's indeed a very complex study, but the good news is that it can be summarized in a way that the general public can easily digest and act upon appropriately in ways to potentially reduce the risk of severe infection.
"In lay terms, our work suggested that the COVID-19 infection can be quite severe under oxidative stress, providing some rationale for the observed greater severity of COVID-19 complications with diabetes and hypertension, both known to cause increased oxidative stress in patients," Bhattacharyay says. "Basically, the receptor protein on our cell surface, as well as those of virus spike proteins known as the 'crown' or 'corona,' are altered under the influence of this oxidative stress, thus allowing the virus protein to attach more tightly and pass its genetic materials to the human cells — the stronger the virus particles can bond to our cells, the worse the infection becomes."
Hati and Bhattacharyay can suggest a few simple lifestyle changes that will help to reduce the amount of oxidative stress in our bodies.
"The things we can do are to get more and better sleep, eat a healthy diet rich in antioxidants and increase exercise," Hati says. "All of these things can reduce oxidative stress, which in turn can potentially reduce severity of COVID-19 infection."
Next steps for faculty and students
As biochemists, the Hati-Bhattacharyay lab of student and faculty researchers study certain fundamental biochemical processes happening in the human body and develop theories to understand these processes at the molecular level. Medical and pharmaceutical professionals could then apply these findings toward their practices and product development.
"The fundamental aspect of this study is to develop an understanding of how the interactive energy between the virus spike protein and the human cell-surface receptor is changing under certain conditions such as oxidative stress and validate these findings through laboratory experiements — that's where the theoretical side and the experimental sides converge," Bhattacharyay says.
As students now work to refine and dive more deeply into the findings of the June publication, there are new goals in mind.
"Our ongoing investigations will hopefully shed more light on the impact of oxidative stress on COVID-19 in the coming weeks," Fossum says. "We haven’t hit any major roadblocks. At the moment we’ve transitioned into more analysis than experimentation in hopes of quickly turning out a paper. We hope to be able to aid in current vaccine development and share our findings with the rest of the scientific community."
The team is set to present their initial findings at the American Chemical Society National Meeting & Expo, a virtual event this year. Additionally, they hope to add preliminary experimental results based on these theoretical findings in order to apply for grant funding from the National Institutes of Health for further research. While as of now there are no external research partners, there are ongoing talks with Mayo Clinic in Rochester, Minnesota, about potential collaborations.
Unique opportunities under extreme circumstances
As Liebau explains, the chance to become part of a COVID-19 research project was not even a known quantity just one semester ago, but it has now placed these lucky Blugolds at the forefront of research into the world's most urgent problem. It took not only the onset of a deadly pandemic, but also the diligence and support of the UW-Eau Claire chemistry faculty to quickly convert a seemingly "lost semester" into this rare opportunity.
"Most of our team was working on experimental rather than computational projects, so when COVID-19 shut down the university, I was very concerned for how I would continue my research," Liebau says. "Both Dr. Hati and Dr. Bhattacharyay have gone above and beyond to make sure that every student from their lab has been able to shift to remote computational work. Since I'm in the process of applying to graduate programs, being able to continue my research during the pandemic and to shift focus to the current outbreak are both unique opportunities that will set me apart from other candidates."
Inserted graphic images: #1 sourced from Centers for Disease Control and Prevention; #2 sourced from Chemical and Engineering News, American Chemical Society.
For more information about the ongoing research in the Hati-Bhattacharyay lab, including lab alumni successes, see this website.
For more information about the Blugold Supercomputing Cluster, visit their website.
Top photo caption: : Dr. Sanchita Hati (left) and Dr. Sudeep Bhattacharyay are shown in their computational lab where the use of computer models and 3D-printed reproduction of proteins to unlock the mysteries of the novel coronavirus known as COVID-19.