RMC-113 a potent small molecule dual inhibitor of lipid kinases PIP4K2C and PIKfyve with binding Kd of 370 nM and 46 nM respectively, potently suppresses the replication of multiple RNA viruses including SARS-CoV-2.
RMC-113 suppresses the enzymatic activity of PIKfyve (IC50=8 nM).
RMC-113 shows IC50 of 392 nM and 299.8 nM for PIP4K2C and PIKfyve in cell-based target engagement analysis via live-cell NanoBRET assays.
RMC-113 displays no activity against PIP4K2A and PIP4K2B, and low or no affinity for other kinases and overall excellent selectivity against 335 kinase panel.
RMC-113 dose dependently inhibits replication of WT and SARS-CoV-2 expressing Nluc-reporter (rSARS CoV-2/Nluc (USA-WA1/2020 strain)) in human lung epithelial (Calu-3) cells, as measured via plaque (EC50=0.25 μM) and luciferase (EC50=1.45 μM) assays, respectively.
RMC-113 also suppresses replication-restricted pseudovirus bearing SARS CoV-2 spike (S) protein (rVSV-SARS-CoV-2-S) in Vero cells (EC50=1.8 μM).
RMC-113 dose-dependently suppressed SARS-CoV-2 replication measured in ALO culture supernatants by plaque assays (EC50=0.15 μM) and nucleocapsid (N) transcript expression measured in ALO lysates by RT-qPCR (EC50=0.35 μM), and CC50 >10 μM.