The FDA-Approved Drug Cobicistat Synergizes with Remdesivir To Inhibit SARS-CoV-2 Replication <i>In Vitro</i> and Decreases Viral Titers and Disease Progression in Syrian Hamsters
Iart Luca Shytaj, Mohamed Fares, Lara Gallucci, Bojana Lucic, Mahmoud M. Tolba, Liv Zimmermann, Julia M. Adler, Na Xing, Judith Bushe, Achim D. Gruber, Ina Ambiel, Ahmed Taha Ayoub, Mirko Cortese, Christopher J. Neufeldt, Bettina Stolp, Mohamed Hossam Sobhy, Moustafa Fathy, Min Zhao, Vibor Laketa, Ricardo Sobhie Diaz, Richard E. Sutton, Petr Chlanda, Steeve Boulant, Ralf Bartenschlager, Megan L. Stanifer, O. Fackler, Jakob Trimpert, Andrea Savarino, Marina Lušić
Abstract
The lack of effective antiviral treatments against SARS-CoV-2 is a significant limitation in the fight against the COVID-19 pandemic. Single-drug regimens have so far yielded limited results, indicating that combinations of antivirals might be required, as previously seen for other RNA viruses. Our work introduces the drug booster cobicistat, which is approved by the FDA and typically used to potentiate the effect of anti-HIV protease inhibitors, as a candidate inhibitor of SARS-CoV-2 replication. Beyond its direct activity as an antiviral, we show that cobicistat can enhance the effect of remdesivir, which was one of the first drugs proposed for treatment of SARS-CoV-2. Overall, the dual action of cobicistat as a direct antiviral and a drug booster can provide a new approach to design combination therapies and rescue the activity of compounds that are only partially effective in monotherapy.