The desktop computers are part of the DataseamGrid, a network of computers housed in classrooms of 48 Kentucky school districts as part of a partnership designed to support research, education and workforce development.

John Trent, PhD, deputy director of basic and translational research at the , conducts virtual screening to discover new cancer drugs using the DataseamGrid for high-volume computations. Today, he has the computers at work 24/7 to identify the most promising drugs and compounds to fight SARS-CoV-2 and its disease, COVID-19.

“In these unprecedented times, we had a resource where we could potentially make an impact quickly and switch over from some of our cancer targets to SARS-CoV-2 targets,” Trent said. “We have been very successful in doing this in cancer for 15 years. We are using the same approach in targeting the coronavirus, just targeting a different protein.”

Established in 2003, is funded by the Kentucky General Assembly to provide computing infrastructure, workforce development and educational opportunities for students and staff in Kentucky school districts. Available computing power in those units is put to work performing computer modeling calculations to screen anti-cancer drugs for Trent’s team and collaborators at UofL.

“Like a lot of industries, we have shifted our skills and infrastructure to address this issue,” said Brian Gupton, CEO of Dataseam. “We are always going to have cancer, but at least for the time being, we are glad the DataseamGrid is here for Dr. Trent to screen those drugs.”

In mid-March, Trent and his team entered new data onto the DataseamGrid, along with UofL’s dedicated research computers, in a two-pronged approach to match three-dimensional models of proteins in SARS-CoV-2 to drugs and compounds that could help in treating or preventing COVID-19. The DataseamGrid provides up to 80 percent of the computational power for these projects.

The first approach is to test about 2,000 drugs already on the market and another 9,000 investigational drugs and nutraceuticals that have been tested for toxicity to isolate those most likely to be effective against the virus.

“For the immediate approach, we are testing drugs that already are approved by the FDA or have been tested in humans. If we find activity with those drugs, we could get them into patient trials a lot quicker,” Trent said. “However, these drugs obviously were designed for something else and they may not have the same efficacy of a very selective drug.”

To find that selective drug, Trent’s second prong of research includes computational models to screen 37 million small molecules and compounds against the target proteins in SARS-CoV-2. These molecules could be used to develop a new drug specifically to treat the virus. That process would take more time, however, to obtain FDA approval.

“That initial discovery of a new, more-selective agent is more long term. You are looking at 12 to 18 months before you would even think about testing those in a patient,” Trent said. “But time is of essence at the moment, so we are doing both things at the same time.”

Using the DataseamGrid and UofL research computers, Trent and his team are screening the drugs and small molecules against 3-D structures of four proteins in the virus to see which compounds might bind with the proteins. A drug that interferes with the activity of any of these proteins would reduce the virus’s ability to spread.

Trent began the research with the first two proteins described for SARS-CoV-2: the main protease, an essential enzyme used by the virus to break down viral proteins and make new virus particles, and spike proteins, the triangular “knobs” the virus uses to attach itself to host cells. These spikes are the knobs commonly seen in graphic images on the surface of the virus. Trent now also is testing drugs against two additional target proteins that were described very recently.

So far, the process has identified about 30 drugs as potentially effective against SARS-CoV-2. Trent recommended these for biological testing by other UofL researchers in the (CPM). Directed by Kenneth Palmer, Ph.D., the CPM is one of only a few labs in the United States capable of testing the drugs against the virus. That testing is expected to begin in mid-April.

If the CPM researchers find the drugs to be effective against SARS-CoV-2 in the lab, they could be moved to the next phase of testing in animal models, testing that also may be conducted at CPM.

“This computer modeling is an excellent way to identify the best potential candidates for laboratory testing rapidly, and this strategy could lead to relief sooner rather than later for patients suffering from COVID-19,” Palmer said.

Gupton says it is good to know the DataseamGrid continues to support urgent medical research even though students are working from home.

“Ironically, we hope to return to cancer research as soon as possible,” Gupton said. “Even though the students are not in classrooms, Kentucky school districts are providing them with instruction, technology, internet access and even meals. The districts’ Dataseam systems engineers are supporting both the university’s work and K-12 efforts. We all are proud to be ‘digital first responders’ in Kentucky’s part of the global fight.”

As part of the Dataseam partnership, UofL provides academic scholarships annually for students from participating school districts who come to the university to pursue a degree in science, technology, engineering or math.

Infectious disease researchers at UofL are working with all 10 Louisville hospitals and two in southern Indiana, including UofL Health, Norton and Baptist, to process tests and study the illness in order to gather information needed to prevent transmission of COVID-19. Julio Ramirez, MD, chief of the Division of Infectious Diseases, and Ruth Carrico, PhD, RN, professor in the division, along with Donghoon Chung, PhD, and Kenneth Palmer, PhD, director of the Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases (CPM), have��developed a surveillance program to track the prevalence of the illness and which patients are most affected.��

“I think the big issue is understanding the emergence of this illness and the pandemic response in terms of where the cases are, how many cases we’re seeing and among what types of patients,” Carrico said. “This study will help us better understand risk factors and how we need to approach it from a preventive perspective,” Carrico said.

Because this virus is so new, health professionals do not have as much information about how the disease presents initially and how it progresses as they do about other diseases that have been studied for decades. They also still need a better understanding of how the virus, SARS-CoV-2, is spread. The work being done at UofL will help provide that knowledge.

“With the information we are gathering, we will better understand how transmission occurs. When we understand how transmission occurs, that provides us the tools we need to develop some effective interventions,” Carrico said.

The development of testing for this research has been led by researchers at the CPM, where Chung worked to establish and refine procedures for high-throughput testing of more than 350 clinical samples per day for the research.

This information is needed not only to protect the community, but to protect health care workers from becoming ill. In China and elsewhere, doctors and nurses contracted COVID-19 at high rates, which affected their availability to care for ill patients. The information gained through the surveillance program will be used to generate guidelines for real-time hospital and community education and response activities, reducing spread in hospitals and protecting health care workers on the front lines.

Over time, the surveillance project will reveal not only the current scope of the pandemic in Louisville and beyond, but will monitor the epidemic over weeks and months, allowing the researchers to predict the impact of the virus in the future.��