Development of TMPRSS2 Antibody as an Antiviral Treatment for SARS-CoV-2 (COVID-19)

To enter a host cell, SARS-CoV-2 uses its spike protein to bind to the ACE2 cellular receptor and then is primed by the type II transmembrane serine protease TMPRSS2. We aim to develop an efficient antiviral via a monoclonal antibody of TMPRSS2, AL20, to impede the entrance of the virus into cells, specifically into lung epithelial cells. This past year is the first year of this funding award and the COVID-19 pandemic and the delayed approval from the HRPO significantly impacted our research activities in a negative way. Despite the challenges and unusual circumstances, we still made progress and determined that there is no cytotoxicity when treated cells with AL20. In addition, we showed that alveolar type II (AT2) cells generated from human pluripotent stem cells (hPSCs) in the2D and 3D lung models were susceptible to both SARS-CoV-2 pseudovirus and live virus. Furthermore, we showed treating with AL20 inhibits the SARS-CoV-2 pseudovirus transduction in Calu-3 cell line and the 2D hPSCAT2 cells. During the next reporting period, we hope to make up the lost time and effort toward completion of the proposed research.