Study to elucidate the mechanisms of inhibiting SARS-CoV-2 (COVID-19) viral entry into the lung epithelial cells
The proteases ACE2 and TMPRSS2 expressed on human lung epithelial cells facilitate the cellular uptake of COVID19 (SARS-CoV-2) via spike proteins and play a major role in their pathogenesis. In this study, a team of scientists led by Hemant Mishra, PhD, Veterinary and Biomedical Sciences, will investigate whether the combinatorial approach of blocking both ACE2 and TMPRSS2 proteases by various means can effectively prevent the cellular entry of the virus.
“The compromised epithelium, after viral entry, can increase susceptibility toward a number of opportunistic infections encouraging a dysregulated immune response which is inefficient in combating with the pathogens. This could also instigate a storm of cytokines in the blood leading to septic shock and/or a decline in the lung functions causing various respiratory distress related disorders etc. Hence, understanding the mechanisms to block the viral entry into pulmonary epithelial cells can greatly assist in the treatment by preventing some of the complications attributed to the higher mortality rate,” said Mishra.
The project collaborators include Bruce Walcheck, PhD, who has years of experience in leukocyte biology and his laboratory will help accelerate these discoveries; Kathleen Boris-Lawrie, PhD, who has vast experience in molecular virology and her lab is well equipped to perform all proposed cell culture-based viral entry assays for SARS-CoV-2; and Gatikrushna Singh, PhD, who has years of experience in developing small molecular inhibitors and pseudovirus propagation and transduction.
The research leads from this study will be utilized in designing several preclinical investigations to further understand the disease pathogenesis and to compete for various federal grants.
This project is supported by the UMN Campus Public Health Officer's CO:VID (Collaborative Outcomes: Visionary Innovation & Discovery) grants program, which support University of Minnesota faculty to catalyze and energize small-scale research projects designed to address and mitigate the COVID-19 virus and its associated risks.