Prepare, test, treat, eliminate
The CVM seeks solutions for COVID-19
- Issue:Published:Photo(s) by:Megan Murrell
Research in the field of veterinary medicine has historically helped advance outcomes for human patients. In these urgent times, the University of Minnesota College of Veterinary Medicine (CVM) is making numerous strides in the fight against COVID-19.
CVM research expands scientific understanding of how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, works. Every day, we move toward identifying ways to defeat this destructive disease as we address the problem from all directions. Our researchers have longstanding expertise in investigating viruses in a number of contexts and are now directing their extensive relevant skills and knowledge to this virus.
Prepare
A closer look at SARS-CoV-2’s genome
Using both commercial reference material and potential clinical samples from the University of Minnesota Medical School, Lions Gift of Sight, and Veterinary Medical Center, a team of researchers led by Declan Schroeder, PhD, will convert a targeted next-generation sequencing approach (that was developed in-house) to sequence SARS-CoV-2. Schroeder's team has a proven track record of successfully sequencing other positive single-stranded RNA viruses such as porcine reproductive and respiratory syndrome virus in swine and deformed wing virus in bees. A closer look at the whole genome of the SARS-CoV-2 from multiple sources will help scientists better understand how it moves, evolves, and functions, which can help predict possible future re-emergence in both humans and animals. It can also be used as a powerful diagnostic tool for screening SARS-CoV-2 directly from various clinical materials.
Informing social distancing measures
Meggan Craft, PhD, associate professor in the Department of Veterinary Population Medicine is collaborating with Eva Enns, PhD, associate professor in the Division of Health Policy and Management in the School of Public Health, to create a model of how the novel coronavirus moves through an individual’s network. This study, funded by the UMN Rapid Response Grant program, aims to help decision-makers anticipate relaxing household isolation while minimizing transmission rebound, mitigating consequent deaths. The scientists will work with decision-makers to leverage insights from the team’s network science to develop clear visualizations of different social distancing scenarios that illustrate which household-to-household interactions best decrease the rate of COVID-19 spread. The goal is to develop a network model to simulate the spread of COVID-19 virus through communities and to test the effectiveness of relaxing social distancing control strategies under different scenarios. Results from this project would provide guidance to decision-makers regarding the timing, implementation, and communication of reducing social distancing measures. This research team's long-developed, tried-and-true methods have allowed them to successfully model countless viruses in both animal and human population networks, including the swine flu, retroviruses in pumas and lions, and raccoon rabies.
Improving COVID-19 transmission modeling
Transmission models of COVID-19 are used by policymakers and hospital leaders to inform disease prevention and mitigation activities and prepare for case surges. For these models to effectively guide public health planning and interventions, they need reliable parameter values that represent the population of interest. But often parameter values are obtained by observations made in other regions or are aggregated at geographical scales that do not account for local mitigation efforts. Amy Kinsley, DVM, PhD, is leading a study that will quantify values associated with the duration of the stages of COVID-19 infection and transmission rates to support state-level modeling efforts. Her study will report trends in transmission rates for each state in the United States to measure the impact of mitigation strategies, including social distancing, shelter in place orders, and the relaxation of those strategies. This project is supported by the UMN COVID-19 Rapid Response Research Grants program.
Test
Accurate, accessible testing
The ability to detect antibodies against a SARS-CoV-2 infection presents a tremendous opportunity for the development of a COVID-19 diagnostic test. Effective, efficient, and accessible diagnostic testing is crucial to mitigate the current pandemic. Yuying Liang, MS, PhD, and Hinh Ly, MA, PhD, have received funding from the UMN COVID-19 Rapid Response Grant program to develop a convenient and cost-effective approach to detecting viral antibodies. Their test would be suitable for screening a large number of samples and would also be sensitive for a more accurate detection of SARS-CoV-2 infection in exposed populations of both humans and animals. They plan to share the results of their work with clinical laboratories at the University of Minnesota and the Minnesota Department of Health. The project began on March 16, 2020 and is slated to wrap up by March 15, 2021.
A handheld option
A team of researchers led by Maxim Cheeran, MVSc, PhD, and Jianping Wang, PhD, in the Department of Electrical and Computer Engineering at the College of Science and Engineering, are developing point-of-care diagnostic tests for COVID-19 that physicians could use at an office visit. This biosensing device would use magnetic particle spectroscopy and giant magnetic resistance technology to detect changes in magnetic response when the virus in the sample binds to the detection reagent. This accurate and highly sensitive technology has been miniaturized into a handheld device that can be easily used at a doctor's office, which will help make testing more widely available to physicians, while reducing the time and expertise it takes to do a test. This project is funded by the UMN COVID-19 Rapid Response Grant program. Several prototypes of the handheld device are expected to be completed by the end of April, at which point researchers will begin test validation.
Treat
Exploring new treatments for COVID-19
SARS-CoV-2 ignites an immune response to infection, which results in severe lung inflammation. A team of researchers led by Maxim Cheeran, BVSc & AH (DVM) MVSc, PhD, and Walter Low, PhD, in the Department of Neurosurgery at the Medical School, are working to develop a unique stem cell therapy to mitigate this particularly life-threatening symptom of the disease. The team will model COVID-19 in animals with hopes of establishing effective methods for human treatment. The scientists involved have previously successfully modeled this approach in animals with brain inflammation from a stroke, which led to human clinical trials. The project began in late March and the first experiments are slated to be completed in May to determine if their stem cell treatment can inhibit lung inflammation.
Managing the body’s immune response to limit SARS-CoV-2 infection
SARS-CoV-2 uses its spike protein to recognize the receptor ACE2 on human lung cells, attaching the virus to the cells. ACE2 expression can be decreased during this process by being clipped from the cell surface by an enzyme called ADAM17, resulting in increased lung damage. ADAM17 also clips other proteins that induce lung inflammation. Bruce Walcheck, PhD, and other researchers are leveraging their extensive experience and resources in immunology and virology research to explore ways to block ADAM17 function. They are hopeful that this approach will reduce various causes of lung damage during infection. If successful, the pilot study will be leveraged for drug development to target ADAM17. Over the next couple of months, the scientists will gain insight on how fast this project might develop.
Targeting a potential Achilles' heel of COVID-19
Proteins of highly pathogenic viruses, such as SARS-CoV-2 that causes COVID-19 disease, play a critical role in the body’s immune response to infection, sometimes causing overt inflammation and tissue damage. A team of scientists led by Qinfeng Huang, PhD, suspects that a viral protein on SARS-CoV-2 — the nucleocapsid (N) protein — might be responsible for dampening the immune response that allows the virus to replicate unchecked. This can then prompt severe inflammation and lung tissue injury. Identifying the protein responsible for this dangerous and unwanted bodily reaction can lead to potential treatment and prevention options against this deadly virus. Huang and his research team in the Ly-Liang laboratory have about a decade of experience investigating the role of key proteins in modulating virus-host interactions by deadly viral infections, including Lassa fever and Ebola. This project is funded by the UMN COVID-19 Rapid Response Grant program, and is slated to wrap up by April 15, 2021.
Eliminate
Striving for a new vaccine
Social distancing can help deter some of COVID-19’s spread, but the development of a vaccine is the only surefire way to combat this devastating disease. A team of researchers led by Hinh Ly, MA, PhD, and Yuying Liang, MS, PhD, has received funding from the UMN COVID-19 Rapid Response Grant program to use their recently patented technology to develop one such vaccine. These scientists have already successfully used this technology to develop a new vaccine against human influenza virus. That vaccine showed 100% protection against lethal influenza infection in a mouse model. Now, they aim to determine whether and how well the new vaccine for SARS-CoV-2 can generate cellular immune responses in vaccinated mice. Funding for this project began on March 16, 2020 and extends through March 15, 2021.
Killing airborne coronavirus
Montserrat Torremorell, DVM, PhD, is collaborating with researchers both within the CVM and at the College of Science and Engineering to test whether air purifying systems can inactivate airborne coronaviruses. The team is using different coronaviruses as surrogates of SARS-CoV-2. If the scientists can effectively inactivate these airborne virions, they intend to directly work with M Health Fairview to implement portable engineering controls in air purification systems within M Health Fairview facilities. Members from this research team have previously used this approach to effectively inactivate airborne porcine reproductive and respiratory syndrome virus and swine influenza virus — viruses with similar characteristics to SARS-CoV-2 — in swine barns. This project is funded by private companies.
Blocking viral entry
Human pulmonary epithelial cells, which serve many important functions in human lungs, express two key enzymes, ACE2 and TMPRSS2, that help SARS-CoV-2 enter human pulmonary epithelial cells. These enzymes facilitate viral entry specifically through their interaction with spike proteins. In this study, a team of scientists led by Hemant Mishra, PhD, will investigate whether blocking ACE2 and TMPRSS2 — by various means — can effectively prevent the virus from entering human cells. Understanding which mechanisms block the virus from entering lung cells can prevent some of the complications attributing to the higher mortality rate associated with the disease, improving treatment for sick patients. With years of experience in leukocyte biology, molecular virology, and the development of small molecular inhibitors in animal models, the team’s labs are well equipped to seek these answers. Their findings will be used to design several preclinical investigations to further understand how COVID-19 develops. The study has received funding from the UMN COVID-19 Rapid Response Research Grants program.
Preventing SARS-CoV-2 from replicating
The COVID-19 outbreak has crystallized the urgent need for therapeutics to better prevent transmission in human populations. Viruses are not living, so they cannot reproduce on their own — they rely on host cells to get the energy, enzymes, and precursors they need to produce the proteins necessary to replicate. So, stopping the virus from being able to generate proteins when it is inside a host cell is fundamental to limiting the development of COVID-19 as well as its transmission. A study being led by Kathleen Boris Lawrie, PhD, will produce lead compounds that restrain SARS-CoV-2 from producing viral proteins, curbing transmission rates. Previously, this team of researchers has gathered preliminary data identifying compounds to reduce virion production of HIV. This work is funded by the UMN COVID-19 Rapid Response Research Grants program. It began in April 2020 and will continue until March 2021.
Clarifying the virus’s bind to human cells
Coronaviruses infect humans by binding to specific proteins, known as receptors, on human cell surfaces. Researchers from the University of Minnesota, led by Associate Professor Fang Li, PhD, recently became the first to use x-ray crystallography, the “gold-standard” method of structural biology at atomic resolution, to map out the 3D structure of a protein on SARS-CoV-2 that binds to its human receptor. This information not only facilitates a better understanding of the infectivity of the virus but also sheds light on its animal origin and provides guidance on vaccine and antiviral drug designs. The study was funded by the National Institutes of Health and was recently published in Nature. The Li Lab has decades of experience investigating coronavirus infection and evolution and developing novel strategies to prevent and treat coronavirus infection. Next, the research team plans to use structural information from this study to develop antibody drugs and vaccines that specifically target the binding of SARS-CoV-2 to its human receptor.
Establishing a safer vaccine option
A study led by Mythili Dileepan, PhD, will use non-infectious virus-like particles to create a vaccine for COVID-19. Relying on these virus-like particles (which mimic the SARS-CoV-2 virus), rather than using the actual virus in a vaccine, could stimulate a protective immune response in the human body without the risk of injecting a live virus mutant as a vaccine that can potentially cause disease in humans. The study is funded by the UMN COVID-19 Rapid Response Research Grants program and is slated to wrap up by April 15, 2021. Dileepan and her team in the Ly-Liang laboratory have several years of experience in developing vaccines to treat diseases in humans and livestock.
Join us in this fight
If you are interested in supporting the College's research into COVID-19, contact Bill Venne, director of development and alumni relations at the CVM, at venne025@umn.edu, or 612-625-8480. Or, click on the button below:
