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GRP-60367 is a first-in-class potent and selective inhibitor of rabies virus (RABV) entry that specifically targets the RABV G protein. GRP-60367 inhibits entry of a subset of RABV strains. Resistance profiling of the chemotype revealed hot spots in conserved hydrophobic positions of the RABV G protein fusion loop that were confirmed in transient cell-to-cell fusion assays. Transfer of RABV G genes with signature resistance mutations into a recombinant VSV backbone resulted in the recovery of replication-competent virions with low susceptibility to the inhibitor.
| Cell Experiment | |
|---|---|
| Cell lines | Mouse neuronal N2a cells |
| Preparation method | Virus yield reduction assays. Mouse neuronal N2a cells (1.5 × 104 cells/well) were seeded in a 96-well plate format and incubated for 24 h. GRP-60367 was added in 3-fold serial dilutions, followed by infection of 6,000 focus-forming units (FFU) (MOI, 0.2 FFU/cell) of virus. Control wells without compound were infected in parallel with the same amount of inoculum. After 60 min, the inoculum was removed and replaced with 100 μl fresh DMEM with (treated) or without (controls) compound. Culture supernatants were collected after 48 h incubation at 34°C, and progeny virus titers were determined on N2a cells. |
| Concentrations | 100 nM, 1 uM, 10 uM, 100 uM, 1000 uM |
| Incubation time | 48 h |
| Animal Experiment | |
|---|---|
| Animal models | |
| Formulation | |
| Dosages | |
| Administration | |
| Molecular Weight | 353.46 |
| Formula | C21H27N3O2 |
| CAS Number | 1309241-34-6 |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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