October 22, 2020
Shortly after the COVID-19 pandemic began, researchers at the University of Chicago launched a number of projects aimed at understanding and addressing the virus. From forging new research partnerships to working on curbing the spread of COVID-19 in underserved communities, scholars have identified methods to address this global crisis. Here are descriptions of just a few of the many COVID-19 research projects currently underway across campus.
In Spring Quarter 2020, the University announced a Big Ideas Generator (BIG) COVID-19 Response Grants program to encourage the development of rapid and innovative responses to help slow the spread of COVID-19, particularly in underserved areas, and to support the development of innovative and scalable solutions. As a result, dozens of scholars are engaged in new cross-campus collaborations.
"The University's response to the scientific and societal challenges posed by the pandemic was swift and multifaceted, and BIG grants were a part of the overall strategy," said Elena Zinchenko, Executive Director of Research Development Support in the Office of the Provost. "The Office of the Provost and the deans committed $500,000 for funding, and we received dozens of proposals. There were also campus-wide webinars on multiple COVID-related research projects with hundreds of faculty joining, and other efforts. But BIG was an important effort to support the projects, and it has already paid for itself in follow-up funding received by the recipients."
One research project, Targeting Viral Host Interactions to Control COVID-19, focuses on the investigation of human cells using expertise gained in various types of cancer studies to try and prevent the virus from taking over healthy cells. It has created a new collaboration among researchers from the Biological Sciences Division, Physical Sciences Division, Pritzker School of Molecular Engineering, and Argonne National Laboratory.
"Viruses can’t work alone," said Marsha Rosner, Charles B. Huggins Professor in the Ben May Department for Cancer Research. "They need the body's immune response, so we are looking to target that process and hopefully find an effective method of combating this virus and other viruses that come along down the line."
The approach adopted by this group is to pre-screen compounds using other coronaviruses to ensure that any compounds identified as prospective leads will be effective across multiple coronaviruses. The viral host interaction team is being led by Rosner; Scott Oakes, Professor of Pathology, who developed a screening facility for a mouse coronavirus; Julian Solway, Walter L. Palmer Distinguished Service Professor of Medicine and Pediatrics, who spearheaded a subgroup focusing on loss of barrier function in the lung as a result of COVID-19; and Nir Drayman, Postdoctoral Fellow in the Pritzker School of Molecular Engineering, who developed the initial screen for compounds using a coronavirus that causes the common cold.
To date, the group has studied 2,000 drugs to see if any of them can successfully inhibit the virus. After identifying 100 drugs known to control machinery inside human cells, the 30 most promising are being tested for their ability to block COVID-19 by a team led by Glenn Randall, Professor of Microbiology, at the Howard T. Ricketts biocontainment facility at Argonne National Laboratory—the only high safety lab in the Midwest that can work with live virus. This group has identified several promising compounds that are currently being tested in animals and could lead to potential human clinical trials.
Another BIG COVID-19 Response Grant project is titled Concerted Chemistry Effort to Develop Therapeutics that Target SARS-CoV-2. Run by the Department of Chemistry’s Bryan Dickinson (Associate Professor), Viresh Rawal (Professor), Scott Snyder (Professor) and Guangbin Dong (Professor), this team is one of a number of research groups on campus looking to use chemical biology to develop therapeutics. It relies on the collective efforts of a variety of scholars—computational scientists, chemical biologists, synthetic organic chemists, and biologists—collaborating for first time.
"UChicago's Department of Chemistry is very strong," Dickinson said. "We know how to make molecules, but we don’t have a very strong drug discovery history here. What we do have is an amazing connection to the Pritzker School of Medicine, and we're trying to take advantage of that expertise to develop antivirals targeting COVID-19."
The process involves a structural biology effort currently underway at Argonne. By capturing structural pictures of viral protein targets, the team then synthesizes lead compounds targeting those proteins, assays their properties, and characterizes how they interact with the protein targets through additional structural studies. The most promising molecules are eventually transferred to Randall’s team at the Ricketts lab for additional testing to see if they work effectively against the virus.
"If a vaccine ends up not being completely curative, or if the virus mutates, then antivirals will become even more important," Dickinson said.
The therapeutics project has also engaged a number of postdoctoral researchers and graduate students, giving them hands-on experience working on an accelerated COVID-19 research project. Researchers hope their results also will inform work targeting future generations of coronavirus.
Both BIG COVID-19 Response Grant research teams stressed the importance of the collaborative nature of these efforts and hope this work will lead to additional research partnerships in other areas across the University. Rosner's group has now expanded to approximately 30 researchers. Investigators include biophysicists, chemists, cancer biologists, virologists, and clinicians caring for patients.
"I personally have never been part of a team this broad," Rosner said. "It's so unique in science, and there’s such a desire to solve this problem as quickly as possible, so people are willing to collaborate more. This is a great model, but a lot of funding mechanisms aren’t designed to support this. We need to mobilize our community to be more supportive of this in terms of resources."
Expanding COVID-19 testing and prevention for the most impacted populations
Many other COVID-19 related research projects are in development, including one that aims to expand testing and prevention among underserved populations. Funded by a National Institutes of Health (NIH) Rapid Acceleration of Diagnostics Underserved Populations (RADx-UP) grant, Community Network-driven COVID-19 Testing of Vulnerable Populations in the Central US, or the C3 project, is a $5 million grant leveraging the existing National Institute on Drug Abuse (NIDA) Justice Community Opioid Innovation Network (JCOIN). By tapping into 40 established academic and community partnerships, this research team can quickly recruit, enroll, and test a large number of community members at eight testing sites as part of an existing network across five states.
John Schneider, Professor of Medicine, Epidemiology, and Social Services Administration, received a JCOIN grant in 2019 to fight opioid addictions in prisons. He also serves as Site Medical Director at Howard Brown Health in Hyde Park, where he has experience contact tracing patients with COVID-19. As part of the C3 project, Schneider is incorporating similar contact tracing practices with criminal justice involved (CJI) and low-income Latino patients who have been exposed to COVID-19.
"Contact tracing is hard," Schneider said. "We're caring for people who are undocumented and have CJI. They may not connect with healthcare providers in a traditional way. At Howard Brown, we did really well when we got rid of the bureaucracy—no IDs, no form to fill out, no security guard asking questions in the clinic. When we got rid of all that, we were testing 100 people per day. It was very quick, the program was spread by word of mouth, and I'm convinced we’ll be able to engage the community again for C3."
C3's testing approach focuses on building trust. By partnering with community groups and staffing test sites with people who live in these neighborhoods, patients will more easily identify with the people they interact with and may be more likely to engage with them after receiving a positive test result. Additionally, C3 combines an evidence-based Social Network Testing Strategy (SNS) with public health messages developed by community partners in an effort to more effectively resonate with these patients. SNS has been widely used in various settings with marginalized individuals, such as substance users, who then recruit their social contacts into testing services. Public health messages specific to each community are developed to combat misinformation about COVID-19 and affirm individual agency.
The project also involves a resource component designed to assist patients who test positive. Low-income patients in these communities often live in multigenerational homes and may lack the ability to self-isolate from family members or access personal protective equipment (PPE). Counselors at C3 testing sites can offer patients food, face coverings, money, or places to shelter, depending on their personal needs.
The ultimate goal of C3 is to recruit higher numbers of people vulnerable to COVID-19 in these two disenfranchised communities. Integration of the study within community testing sites are currently being set up, and the 12-month randomized-controlled trial will begin in early 2021. The research team’s goal is to recruit 2,500 participants.
"As a University, we need to really go out into the community and engage when something like this happens, and share the resources we have at our disposal," Schneider said. "Even a negative test is a way to get someone engaged with our system, share accurate prevention information and build trust."
Additional grants related to COVID-19 research
The University continues receiving grants to support COVID-19 research. In September 2020, the Chicago Biomedical Consortium awarded $1.5 million to three Chicago-based, cross-institutional research teams. Each team includes a principal investigator from UChicago.
Research projects include Targeting Aberrant Immune Responses in Patients with Severe COVID-19 (Gokan M. Mutlu, Professor of Medicine and Chief, Section of Pulmonary and Critical Care Medicine at UChicago Medicine); Novel Strategies for Enhancing Vaccine Efficacy Against SARS-CoV-2 (Melody A. Swartz, William B. Ogden Professor of Molecular Engineering and Deputy Dean for Faculty Affairs in the Pritzker School of Molecular Engineering); and Covalent Inhibitors of the Nsp16 2′-O-Methyltransferase of SARS-CoV-2 (Viresh Rawal, Professor of Chemistry in the Physical Sciences Division). The teams each received $500,000 to fund their projects.