Joyce Jose, assistant professor of biochemistry and molecular biology at Penn State, has been awarded seed funding from the Huck Institutes of the Life Sciences at Penn State to apply her expertise in studying potentially deadly viruses to developing targeted therapeutic intervention strategies against SARS-CoV-2, the virus that causes COVID-19.
Jose is a virologist with extensive experience working with biosafety level 3+ (BSL-3+) pathogens, including the West Nile virus. Working directly with these pathogens, which can cause serious and potentially lethal disease through inhalation, requires a bio-containment facility. BSL-3 laboratories are relatively rare at universities, but in 2014 Penn State opened the Eva J. Pell ABSL3 Laboratory for Advanced Biological Research to facilitate this vital research. Jose and her research team have been working in the Pell Lab since 2018, but her proposed research with SARS-CoV-2 will start in her BSL-2 lab using non-pathogenic virus proteins that can be made in cell culture using synthetic DNA constructs.
“We developed at strategy where we can safely fast-track tests for antiviral agents against SARS-CoV-2 and develop a system to evaluate potential vaccine candidates in our BSL-2 laboratory before moving to the BSL-3 lab,” said Jose.
Jose will use synthetic DNA to make cells grown in the lab produce two SARS-CoV-2 proteins that are required by the virus for replication. She can then test the ability of small molecules to inhibit the activity of these proteins. Her team will begin by testing small molecules that are already in use as antivirals against other viruses and have been shown to have low levels of toxicity to human cells, in the hopes of identifying an antiviral agent that could be effective against SARS-CoV-2 and can be developed and approved relatively quickly.
Jose’s team can also trick cells into making the four main proteins that compose the structure of the virus’ outer shell and then assemble the proteins into particles that look, from outside, just like the virus, but lack the ability to cause disease. These virus-like particles can then be used to test the efficacy of potential vaccine candidates before testing the vaccines against the actual virus in the BSL-3 lab.
“Compared to the viruses I am used to working with, the SARS-CoV-2 has an extremely large and complex genome,” said Jose. “In addition to trying to develop strategies to stop its spread as quickly as possible, we also want to begin building genetic systems that allow us to better understand how this virus works. This knowledge can facilitate our understanding of the virus’ pathogenesis, which will be required for the development of future therapeutics and vaccine candidates.”
About the Coronavirus Research Seed Fund
On March 3, the Penn State Huck Institutes of the Life Sciences launched a rapid-response, internal call-for-proposals across the University to address the emerging COVID-19 outbreak, with support from the Materials Research Institute, Social Sciences Institute, Institutes for Energy and the Environment, and the Institute for Computational and Data Science.
Over the course of five weeks, units across Penn State stepped up to assist. To date, more than 120 faculty members in 45 research teams from across eight colleges at Penn State have been granted an overall $2.25 million in seed funding to initiate their vitally important work.
The projects span six core areas: Diagnostics and Detection, Therapeutics and Vaccines, Transmission-blocking Interventions, Social Sciences, Cohort Studies, and Predictive Modeling.