Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L
Anneliese S. Ashhurst, Arthur H. Tang, Pavla Fajtová, Michael C. Yoon, Anupriya Aggarwal, Max J. Bedding, Alexander Stoye, Laura Beretta, Dustin Pwee, Aleksandra Drelich, Danielle Skinner, Linfeng Li, Thomas D. Meek, James H. McKerrow, Vivian Hook, Chien‐Te K. Tseng, Mark Larance, Stuart Turville, William H. Gerwick, Anthony J. O’Donoghue, Richard J. Payne
Abstract
values in the nanomolar range. Reduced antiviral activity was observed in cells overexpressing transmembrane protease, serine 2 (TMPRSS2); however, a synergistic improvement in antiviral activity was achieved when combined with a TMPRSS2 inhibitor. These data highlight the potential of cathepsin L as a COVID-19 drug target as well as the likely need to inhibit multiple routes of viral entry to achieve efficacy.