Philadelphia – An interdisciplinary team within Penn Dental Medicine is conducting research to explore the potential for identifying a novel therapeutic approach to mitigate SARS-CoV-2, or COVID-19, infection. The study, led by principal investigator Dr. Bruce Shenker, Professor in the Department of Basic & Translational Science, was awarded funding as part of a National Institutes of Health (NIH) program to support supplemental COVID-19-related research, receiving a one-year grant extension to Dr. Shenker’s RO1 grant titled “Bacteria and lymphocyte suppression in periodontitis.”
Dr. Shenker and his co-investigators propose that their findings will provide the groundwork for developing a novel, alternative, and potentially transformative therapeutic approach to mitigate SARS-CoV-2 infection. Working with him as co-investigators are Dr. Gary Cohen, Professor, Department of Basic & Translational Science, and Dr. Kathleen Boesze-Battaglia, Professor, Department of Basic & Translational Sciences and Assistant Dean for Academic Initiatives.
The proposed study is based on observations that Dr. Shenker’s group have made regarding the role of a host cell protein, cellugyrin, which they propose plays a role in the host response to microbial virulence factors, such as the cytolethal distending toxin. This new COVID-19-related study is building on these recent observations which may help identify early events associated with viral entry and thereby provide a basis for novel therapeutic pathways for preventing SARS-CoV-2 infection.
“To contain the SARS-CoV-2 infection, it is important to identify early molecular mechanisms that contribute to its high infectivity, as these likely also represent attractive targets for therapeutic intervention,” explains Dr. Shenker. “In our previous work, we have identified a novel role for a host cell protein, cellugyrin. We propose that cellugyrin is a major component of a universal endocytic process utilized by both virus and exotoxins to achieve entry into host cells. This proof-of-principle study is aimed at demonstrating a key role for cellugyrin in the pathogenesis of SARS-CoV-2 infection of cells within the oral-respiratory tract.”
Recent studies have indicated that oral epithelial cells express ACE2 and may be a target for SARS-CoV-2 infection. Therefore, in addition to lung cells, this study is also focusing on human oral epithelial cells lines, including those in the tongue, gingiva, and floor of the mouth.
The study will provide a more robust understanding of SARS-CoV-2 pathogenesis, examining the role of oral/nasal microbiota and ACE2 receptor on SARS-CoV-2 infectivity in oral fluids and nasal secretions, as gateways to the spread of infection into the respiratory tract.