A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells
Matthew Mahoney, Vishnu C. Damalanka, Michael A. Tartell, Dong hee Chung, André Luiz Lourenço, Dustin Pwee, Anne E. Mayer Bridwell, Markus Hoffmann, Jorine Voss, Partha Karmakar, Nurit P. Azouz, Andrea M. Klingler, Paul W. Rothlauf, Cassandra E. Thompson, Melody Lee, Lidija Klampfer, Christina L. Stallings, Marc E. Rothenberg, Stefan Pöhlmann, Sean P. J. Whelan, Anthony J. O’Donoghue, Charles S. Craik, James W. Janetka
Abstract
Significance MM3122 represents an advanced lead candidate for clinical development as a novel antiviral drug for COVID-19. In addition to being novel drugs, these selective TMRSS2 inhibitors can be used as valuable chemical probes to help elucidate mechanisms of viral pathogenesis. Since TMPRSS2 plays a key role as a viral protein processing protease in the pathogenesis of other coronaviruses (SARS-CoV, MERS-CoV) as well as influenza viruses, MM3122 and this class of TMPRSS2 inhibitors hold much promise as new drugs to not only treat SARS-CoV-2 infections but also potentially represent broad-spectrum antivirals.