Marwah Karim, Manjari Mishra, Chieh-Wen Lo, Sirle Saul, Halise Busra Cagirici, Do Hoang Nhu Tran, Aditi Agrawal, Luca Ghita, Amrita Ojha, Michael P East, Karen Anbro Gammeltoft, Malaya Kumar Sahoo, Gary L Johnson, Soumita Das, Dirk Jochmans, Courtney A Cohen, Judith Gottwein, John Dye, Norma Neff, Benjamin A Pinsky, Tuomo Laitinen, Tatu Pantsar, Antti Poso, Fabio Zanini, Steven De Jonghe, Christopher R M Asquith, Shirit Einav
In search for broad-spectrum antivirals, we discovered a small molecule inhibitor, RMC-113, that potently suppresses the replication of multiple RNA viruses including SARS-CoV-2 in human lung organoids. We demonstrated selective dual inhibition of the lipid kinases PIP4K2C and PIKfyve by RMC-113 and target engagement by its clickable analog. Advanced lipidomics revealed alteration of SARS-CoV-2-induced phosphoinositide signature by RMC-113 and linked its antiviral effect with functional PIP4K2C and PIKfyve inhibition...
April 17, 2024: bioRxiv