Awarded Projects:
1. Bradley Berron, PhD
UK College of Engineering
Hand Sanitizer Production: Bottleneck Analysis and Remediation
Kentucky’s distilleries have stepped up to address hand sanitizer shortages by blending and bottling sanitizer for hospitals, schools, testing centers, and essential businesses. Researchers are now testing cleaning methods to ensure that food-safe bittering agents used in hand sanitizer do not remain in distillery equipment when they transition back to production of their signature products. This research will be conducted by the team at UK’s James B. Beam Institute for Kentucky Spirits. Brad Berron, College of Engineering, and Seth DeBolt, College of Agriculture, Food and Environment, will develop cleaning strategies and Bert Lynn, College of Arts and Sciences, will test for traces of bittering agents.
2. Scott Berry, PhD
UK College of Engineering
Optimization and Validation of a Point-of-Care Serology Test for COVID-19
SARS-CoV-2 serological assays, which measure antibodies made against the virus and indicate prior exposure and potentially immunity to further infection, are critical for identifying individuals who may be at continued risk of infection and require enhanced protection. Unfortunately, the “gold standard” technology for testing, known as ELISA, is difficult to perform and typically requires advanced equipment that is unavailable in many areas, particularly in rural regions. Therefore, the goal of this project is to develop a simplified high-sensitivity serology test. To achieve this, we will leverage a new technology known as Exclusion-based Sample Preparation (ESP), which has previously been used to substantially simplify other molecular assays.
3. Louis Hersh, PhD
David Rodgers, PhD
UK College of Medicine
Production of Single Chain Antibodies (Nanobodies) to SARS-CoV-2 Spike Glycoprotein and its Receptor Binding Domain
There are currently no approved vaccines, drugs, or antivirals to treat COVID-19, although a number of such agents are currently being developed and tested. One treatment for COVID-19 is the use of convalescent plasma containing antibodies against the virus (passive immunity) (Chen et al., 2020, Casadevall A and Pirofski LA (2020, Bloch et al., 2020). An alternative form of passive immunity is the use of single chain antibodies (nanobodies) that inhibit the binding of the virus to its target cell referred to as “neutralizing nanobodies”. Nanobodies exhibit the same high affinity for their target protein as conventional antibodies, however their small size (~15 kDa vs ~150 kDa for conventional antibodies) makes them more stable and permits them to be expressed at high levels at a low cost. In addition, nanobodies can be “humanized”, exhibit low immunogenicity and can be inhaled for delivery to the lungs. Thus, a nanobody that blocks the binding of the SARS-CoV-2 S protein to its receptor could be an effective therapeutic to treat COVID-19. Alternatively, a nanobody that prevents ACE2 receptor-mediated uptake of the virus would also be a valuable therapeutic. Nanobodies have proven to be effective agents to disrupt protein interactions and functions. Thus, the objective of this proposal is to generate nanobodies to the SARS-CoV-2 spike protein (S protein) and to its receptor binding domain (RBD) with a focus on defining nanobodies that have the potential to act as neutralizing nanobodies.
4. James Keck, MD, MPH
UK College of Medicine
WACKY: Wastewater Assessment for Coronavirus in Kentucky (co-funded by UK-CARES)
Wastewater-based epidemiology (WBE) is a SARS-CoV2 surveillance strategy that evaluates wastewater for the presence of viral biomarkers, like viral RNA. To streamline WBE, we will adapt new technology called Exclusion-based Sample Preparation (ESP), which provides a fast, simple, and electricity-free means of manipulating RNA. As a secondary objective, we will assess the environmental stability of SARS-CoV2 RNA in wastewater under various environmental conditions to inform the sensitivity of WBE for SARS-CoV2 surveillance. Our technology has the potential to improve WBE sensitivity, promote its localized deployment, such as at congregate living settings, and support environmental surveillance in low resource settings.
5. Bruce O'Hara, PhD
UK College of Arts and Sciences
Development of Noninvasive Cage-Based Breath Tracking for Mouse Models of COVID-19
Animal models are critical to develop improved treatments for COVID-19, ranging from anti-viral drugs and vaccines, to the reduction of damage from mechanical ventilation. Rodents are generally the first animals tested, however, a major limitation is the lack of easy to use technology for the assessment of breathing. Drs. Bruce O’Hara and Kevin Donohue previously developed a simple, noninvasive method to assess sleep in rodents using piezoelectric sensors, and their PiezoSleepTM system is now used worldwide in preclinical studies. In this proposal, they team with Dr. Chris Waters to adapt their technology to COVID-like respiratory illnesses.
6. Daniel Pack, PhD
UK College of Engineering and Pharmacy
Proton-Sponge Polymers for Inhibition of SARS-CoV-2 Infection
The goal of this project is to investigate polymers with high buffer capacity as inhibitors of SARS-CoV-2 infection. We hypothesize that these “proton sponges,” originally developed for delivery of nucleic acids to cells, will prevent pH-dependent fusion of viral and cell membranes, preventing the virus from entering cells. Repurposing proton sponges as antivirals targeting a host factor exploited by numerous viruses may represent a new class of compounds for fighting COVID-19 as well as other existing and emerging viral diseases.
7. Christina Stowe, PhD
UK College of Agriculture, Food and Environment
Kentucky's Equine Markets Amidst COVID-19: Community Impacts
Kentucky is the self-proclaimed “Horse Capital of the World,” and Kentucky’s equine industry is a major contributor to the state’s agricultural economy. This project will estimate market impacts of COVID-19 restrictions in different segments of the equine industry. Results will inform recovery efforts as well as decision-making and preparedness to protect the viability of equine operations against future market contractions. In addition, this project will provide the framework to better understand the impact of COVID-19 on equine markets at a national level.
8. Steven Van Lanen, PhD
UK College of Pharmacy
RNA-Dependent RNA Polymerase as an Antiviral Target
NEW HIGH THROUGHPUT ACTIVITY-BASED SCREEN FOR RNA-DEPENDENT RNA POLYMERASES Nucleobase/nucleoside analogues, including remdesivir, EIDD-1931 (β-D-N4-hydroxycytidine), and favipiravir, have demonstrated excellent promise for treating SARS-CoV-21-3. Remdesivir is currently being tested in ten clinical trials to treat SARS-CoV-2 (and one to treat Ebola) 4. Favipiravir is approved in Japan to treat influenza5-8 and is also being tested in multiple, independent clinical trials for SARS-CoV-2, Ebola, and influenza4. These nucleobase/nucleoside analogues target RNA-dependent RNA polymerase (RdRp) thereby interfering with RNA replication and metabolism9. RdRp is unique to positive-sense, single-strand RNA (pssRNA) viruses that includes coronaviruses, ebolaviruses, influenza viruses including pandemic influenza A (H1N1), enteroviruses (polio- and rhinoviruses), flaviviruses (yellow fever and West Nile), among others7,8. Within the past two weeks, multiple groups have reported the production of recombinant RdRp and the auxiliary proteins from SARS-CoV-2, and activity tests have confirmed that remdesivir and favipiravir—following metabolism to the nucleoside-5’-triphosphate—interfere with RNA replication by dually serving as alternative substrates and inhibitors10-12. Current evidence suggests RdRp, which is essential for the replication of the RNA in pssRNA viruses and has no homologs in mammals, is a viable target for antiviral drug discovery. The major limitation in the discovery and development of therapeutics that target RdRp is the very low throughput of existing activity-based assays. In this proposal we will develop a novel, universal assay for assessing RdRp activity. The assay will be used to thoroughly characterize SARS-CoV-2 RdRp and to implement, for the first time, a relatively high throughput activity-based screen for testing the CPRI’s synthetic compound and natural product library for inhibitors, alternative substrates, modulators, or effectors of SARS-CoV-2 RdRp activity. Importantly, the methodology can be readily adapted for RdRp from other pssRNA viruses in an effort to identify therapeutics against a broad spectrum of pandemic-causing viruses including SARS-CoV-2.
9. Jerold Woodward, PhD
Siva Gandhapudi, PhD
UK College of Medicine
Identification and Characterization of Virus Specific T Cells in Humans Exposed to SARS-COV-2
In this study, we propose to use the ELISpot assay to identify T cell epitopes in SARS-CoV-2 envelope, membrane, and nucleocapsid proteins that are presented to CD4 and CD8 T cells in SARS-CoV-2 exposed individuals and characterize the T cell responses mounted in SARS-CoV2 exposed individuals.
10. Yuqing Zheng, PhD
UK College of Agriculture, Food and Environment
Acquiring Latest Scanner Data to Study the Impact of COVID-19 on Food Access
We aim to acquire the latest Nielsen scanner data to examine (1) how the COVID-19 has affected the retail meat prices and spending and (2) what is the magnitude and duration of the panic buying or stockpiling behavior toward meat products. For alcoholic beverages, we will specifically assess (3) the dynamic consumer responses in alcoholic beverage purchases and investigate (4) the abnormal impact of the COVID-19 on Corona beer. This study could bring theoretical advancement on the rationality of consumer preferences in responses to income shock or public health crisis, and lead to novel findings that will help to shape these industries going forward.
