COVID-19 Research at MolES

June 3, 2020

In response to the COVID-19 pandemic, MolES faculty have pivoted their research to address the novel coronavirus, SARS-CoV-2. They are leveraging molecular engineering approaches and tools to develop improved diagnostics, targeted treatment strategies, and a better understanding of the virus. We've highlighted a few of these projects below.

Designing targeted treatments for COVID-19

For his doctoral work, Brian Coventry, a molecular engineering graduate student in biochemistry professor David Baker's lab, is designing de novo proteins that bind target proteins with high affinity and specificity. Through the use of DNA chip technology, FACS sorting, and NextGen sequencing, Coventry tests up to 100,000 potential protein binders simultaneously. To date, he and his colleagues at the Institute for Protein Design have successfully designed protein binders for ten natural targets. Using this approach, Coventry and his IPD colleagues are now designing proteins that can bind to either the spike proteins present on the SARS-Cov-2 virus or ACE2, the human receptor the virus binds to in order to get inside the cell and begin replicating itself. These binders could potentially be used as therapeutics, preventing the virus from infiltrating cells by blocking interactions between the spike protein and ACE2.

Bioengineering professor Suzie Pun's lab develops bioinspired materials to advance drug delivery and molecular imaging technologies. Like the Baker lab, researchers in the Pun lab are also targeting the SARS-Cov-2 spike protein, but instead of designing synthetic protein binders, they are developing DNA aptamers, short pieces of DNA that selectively bind to a specific target. Pun received a grant from the Population Health Initiative to pursue DNA aptamers that bind with high affinity to the SARS-CoV-2 spike protein. In addition to potential therapeutic applications, DNA aptamers could also be used in diagnostic devices to quickly and sensitively determine the relative amount of intact virus in patient and research samples.

MolES director and bioengineering professor Pat Stayton's lab has been developing a new class of therapeutic treatments called "drugamers" designed to target places in the lung where pathogens reside, focusing drug exposure where it is needed most and avoiding toxic side effects. Using the drugamer platform, existing antibiotics can be repurposed to effectively treat antibiotic resistant bacteria in preclinical models of disease. Stayton's lab is now attempting to adapt the drugamer platform to deliver antiviral drugs to treat COVID-19 patients. Current antiviral therapies are administered either through an IV, which requires hospitalization and significant healthcare resources, or orally, which has limited efficacy in the lung and comes with potential toxic side effects. In contrast, drugamers can be administered by nebulizers that allow the drug to be inhaled directly into the lung. Mass distribution of "puffer" devices could stem transmission and reduce the seriousness of infections, while protecting early responders and caregivers.

Testing for COVID-19

Professor Barry Lutz's lab in Bioengineering develops diagnostics for infectious diseases, with a focus on rapid, easy-to-use tests that can be run in non-laboratory settings such as small clinics, community sites, or even at home. Dr. Lutz collaborates with Dr. Matthew Thompson of Family Medicine as a part of the Seattle Flu Study (SFS), a collaborative research project led by genome sciences professor Jay Shendure to detect, monitor and control the flu in Seattle. Last year, researchers on the Lutz/Thompson team put together flu test kits that were mailed to people at their homes, allowing them to self-collect a sample and return it back to the lab. When SFS pivoted to become the Seattle Coronavirus Assessment Network (SCAN) to officially serve the Public Health response to COVID-19, the Lutz/Thompson team began making similar testing kits for SARS-CoV-2. Lutz and Thompson are working to develop symptom-based predictions of COVID-19 to aid diagnosis and to design at-home studies to evaluate COVID self-tests as companies develop them. In addition, Lutz' lab is developing their own point of care test using a low-cost device that can detect SARS-CoV-2 RNA in less than 45 minutes and is simple enough for community settings or home use. They are working to pursue FDA authorization and scale up productions to help test scale up in the US and other countries. 

Electrical and computer engineering professor Eric Klavins developed Aquarium a framework for representing lab protocols as executable computer code to improve the reproducibility of experimental protocols and standardize data documentation. This software has previously been used by Klavins' collaborator Barry Lutz to enable minimally trained technicians to reliably run HIV diagnostic tests in low resource settings like Kenya. Through a grant from DARPA's Synergistic Discovery and Design (SD2) program, the Klavins lab is now working with collaborators at Boston University and Duke University to adapt this software to address the huge unmet demand for COVID-19 diagnostic testing. Academic labs may have the physical capacity to do such testing, but most do not have the procedural knowledge necessary to actually carry out testing. The Aquarium software could help labs that are not clinical diagnostic labs, quickly shift to perform diagnostic testing or evaluate the effectiveness of different diagnostic tests as they become available. Aquarium also provides a convenient way to publish complete data sets including data from experimental controls and validation experiments to a cloud-based repository that could be comprehensively analyzed, allowing researchers to spot reliability problems with tests much more quickly.

Understanding SARS-Cov-2

As a molecular engineering graduate student in Jens Gundlach's lab, recent graduate Ian Nova developed a new high-resolution technique to visualize individual proteins processing DNA in real-time. The Gundlach lab is using this technique to study the SARS-Cov-2 helicase and RNA polymerase enzymes in order to better understand how the virus works and inform the design of new therapeutics. Inhibitors to the SARS-Cov-2 RNA polymerase are already being developed as potential therapeutics for COVID-19. High-resolution visualizations of this polymerase in action could help to tease out the mechanism of inhibition.

For more news about how UW researchers are addressing the COVID-19 pandemic visit https://www.washington.edu/news/tag/covid-19/