Researchers at Pritzker Molecular Engineering have dedicated their labs and resources to pressing research questions surrounding the global pandemic of COVID-19.
These multidisciplinary projects focus on approaches to detecting and treating the virus, screening vaccines and antibodies, determining the efficacy of protective equipment, and more.
To meet the high demand of detecting COVID-19 and monitoring the antibody responses in infected patients, the groups of Jun Huang and Junhong Chen are collaborating with Kathleen Beavis (Department of Pathology) to develop an electrochemical detection device capable of both that can be economically produced and administered at home and point-of-care. The technology is expected to be sensitive, precise, reliable, high-throughput, and economic (~$10 per test) for rapid detection (5 minutes) in various specimen from patients (e.g., nasal and sputum samples).
The de Pablo group is using molecular models and advanced computational methods to screen promising drugs that interfere with the SARS-CoV-2 virus cell-attachment mechanism and with its replication process. Their efforts have primarily focused on high-throughput screening of existing drugs that could be repurposed to treat SARS-CoV-2, followed by extensive modeling of promising candidates to understand and potentially improve their efficacy. A parallel effort has sought to understand the Spike protein of SARS-CoV-2, and the key differences with SARS-CoV that make the former virus more effective.
The Esser-Kahn group is developing vaccines against COVID-19 that employ novel molecules. These molecules have two unique advantages over other vaccine candidates. First, they improve the safety of the vaccine by independently modulating the amount of inflammation that is induced by vaccination. Second, they elicit distinct antibodies which could yield better, more effective vaccination through the generation of a broader antibody response.
Quick turnaround testing of the efficacy of cloth masks in filtering particulates covering 10 nm to ~ micron diameter distributions
The Center for Disease Control (CDC) and White House have recommended the use of cloth masks. Consequently, large numbers of people have begun using cloth masks, many of them homemade. However, there is very little data on the efficiency of various fabrics used in cloth masks in filtering particles in the relevant range (10 nm to few microns). Such data, provided it is reliable and available on the scale of days to a week, will be of high value to the public in making their choices. At the University of Chicago and Argonne National Laboratory, the Guha Group is well equipped to carry out and analyze these measurements, and they have begun experiments at the Center for Nanoscale Materials at Argonne National Laboratory, collaborating with respirator measurement specialists at Argonne. They are working round the clock analyzing various types of cloths and hybrid combinations of them, as well as analyzing the role of gaps between the mask and facial contours (a key issue for cloth masks without elastomer fittings).
To better understand the infection of SARS-CoV-2 to host cells, the Huang Lab will measure the infection rate of SARS-CoV-2 to host cells. The measurement systems can also serve as a universal platform for testing the efficacies of different vaccines, antibodies, and small molecule drugs in vitro. In addition, they aim to engineer a new nanoparticle to neutralize the SARS-CoV-2. This new nanoparticle will be tested by their pseudovirus and the real SARS-CoV-2.
From previously infected COVID-19 patient PBMCs, the Huang Lab with that of Patrick Wilson (Department of Medicine) will isolate specific B cell and sequence them to generate a repertoire of B cell receptors to make monoclonal antibodies. These antibodies will be tested for binding to viral proteins and for determining if they have protective activities against the SARS-CoV-2. These antibodies will be valuable as possible therapeutic agents or for the production of high sensitivity and high specificity diagnostic reagents.
COVID-19 is associated with acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC), both of which greatly increase morbidity. The Hubbell Lab has developed an approach to target biologic drugs to the inflamed lung. Here, they are applying that technology to target both blockers of pro-inflammatory cytokines and anti-inflammatory cytokines to the lung in COVID-19, working with the group of Patrick Wilson (Department of Medicine). They are also engineering proteins to blunt the coagulation disorders that result from infection and induce DIC.
Although vaccines for SARS-CoV-2 are currently in development in industry, with at least one already in clinical trials, these vaccines are not guaranteed to function as desired, especially in patients with limited immune responses, such as the elderly. The Hubbell and Swartz Labs are collaboratively developing two nanomaterial vaccine platforms that they have shown can induce very broad neutralizing antibody responses in preliminary work with Lassa virus and malaria antigens.
Neutralizing antibodies are one the natural defenses of the human body that work by blocking a virus such as COVID-19 from infecting cells and spreading. The time needed for the human body to produce antibodies is about a week after the initial infection. Many people may be unable to make effective antibodies on their own, which may explain persistent and severe infections in patients. In collaboration with scientists at the Washington University at St. Louis, the Mendoza Group is identifying antibodies including those isolated from COVID-19 patients, evaluate their potency, and then engineer them to be more potent neutralizing antibodies for use as a drug to prevent infections or minimize the severity and fatality of COVID-19 infections.
Many central regulators of gene expression also impact expression of viral genes, limiting viral replication. Here, the Swartz and Hubbell Labs seek to develop drug formulations to efficiently target gene expression regulators to the airway epithelium, focusing on compounds that may modulate viral replication of SARS-CoV-2 and the effects thereof, such as expression of proinflammatory cytokines.
A successful vaccine against SARS-CoV-2 will generate a repertoire of potent neutralizing antibodies against multiple sites on the viral surface, thus rendering it unable to infect new cells.
Comprised of antigen, adjuvant, and a delivery vehicle, these vaccine variables will affect the antibody response in ways that are currently unpredictable. Here, the Swartz Lab is collaborating with group of Anne Sperling (Department of Medicine, Section of Pulmonary and Critical Care Medicine) and will develop and validate a novel in vitro platform that allows analysis of immune responses to predict outcomes in humans, using human spleen biopsies from an existing tissue bank, for testing vaccine formulations, and use it to compare antibody responses in promising vaccine candidates.
It is critical to rapidly discover drugs that prevent viral infection of human lung cells. Currently, drug screening experiments on live virus can only be implemented in special biocontainment facilities. The Tay Lab has developed a high-throughput microfluidic combinatorial drug screening platform that can measure drug effects on millions of live-cell experiments in a day. They will first repurpose this system for coronavirus drug screening using a model organism. The system will then be transferred to BSL3 facility at Howard Taylor Ricketts Laboratory for screening 5,000 FDA approved compounds on co-cultures of live SARS-Cov-2 and human lung cells to discover new drugs for prevention and treatment of COVID-19.
The Tay Lab is using ultrasensitive nucleic acid measurements via digital-PCR for detection of coronavirus in human saliva samples. Saliva is a preferred sample for virus detection tests, and recently it has been proposed that saliva testing can be a less invasive and massively scalable alternative to currently used nasal swab testing. They are collaborating with Nishant Agarwal (Otolaryngolocy, Head and Neck Surgery, University of Chicago) and Evgeny Izumchenko (Section of Hematology/Oncology, University of Chicago) to determine if saliva testing (retrieved from patients at UC Hospital) can be a useful alternative in the clinic and developing the experimental and computational pipeline necessary for digital-PCR based saliva testing on COVID-19 patients.
While it is known that SARS-Cov-2 can be transmitted by air via large droplets emitted from cough and sneezing of patients, it is not clear if fine aerosols emitted from patients during talking and breathing can transmit this disease. The Tay Lab is collaborating with Jay Pinto (Otolaryngology, Head and Neck Surgery, University of Chicago) to determine if such fine aerosols contain live virus, and to determine the airborne viral load at different distances from COVID-19 patients at the University of Chicago Hospital. Their results will provide immediate guidelines for social distancing and for the effective use of personal protection equipment (PPE) in hospital and social settings.
Acute respiratory distress syndrome (ARDS), caused by widespread blood vessel barrier disruption and uncontrolled cytokine storm, is the major cause of death in COVID-19 patients. Promoting blood vessel health in the lung, although challenging, provides an attractive strategy to treat critically ill COVID-19 patients. We demonstrated that reduction of Krupple-like factor 2 (KLF2, a transcription factor) in pulmonary blood vessels is a major molecular signature of ARDS. Matthew Tirrell (PME) and Yun Fang (Department of Medicine) have engineered a targeted polyelectrolyte complex micelle platform to increase KLF2 in the blood vessels. Currently, we are testing the therapeutic effectiveness of this novel nanomedicine approach in treating ARDS in animal models.