PIKfyve-specific inhibitors restrict replication of multiple coronaviruses in vitro but not in a murine model of COVID-19

• DOI: 10.1038/s42003-022-03766-2
• Publication Date: 2022-08-12T10:05:50Z
• Authors: James Logue; Arup R. Chakraborty; Robert Johnson; Girija Goyal; Melissa Rodas; Louis J. Taylor; Lauren Baracco; Marisa E. McGrath; Robert Haupt; Brooke A. Furlong; Mercy Soong; Pranav Prabhala; Viktor Horvath; Kenneth E. Carlson; Stuart Weston; Donald E. Ingber; Melvin L. DePamph...; Matthew B. Frieman
• Keywords: Pandemic; Coronavirus; 2019-20 coronavirus outbreak

Abstract The ongoing COVID-19 pandemic has claimed more than 6 million lives and continues to test the world economy healthcare systems. To combat this pandemic, biological research community shifted efforts development of medical countermeasures, including vaccines therapeutics. However, date, only small molecules approved for treatment in United States are nucleoside analogue Remdesivir protease inhibitor Paxlovid, though multiple compounds have received Emergency Use Authorization many currently being tested human efficacy trials. One such compound, Apilimod, is considered as a therapeutic Phase II trial. at time writing, there no published data trials or animal models. Here we show that, while Apilimod other PIKfyve inhibitors potent antiviral activity various cell lines against coronaviruses, these worsen disease murine model when given prophylactically therapeutically.