MTDB-imi6 degrader in vivo activity
against SARS-CoV-2 infection in K18-hACE2 mice. (a) Eight- to 12-week-old
female K18-hACE2-transgenic mice were intranasally infected with 104 plaque-forming units (PFU) of SARS-CoV-2 and treated intranasally
1 h preinfection and 3 h postinfection with MTDB-imi6 (25 mg/kg) (n = 6), MTDB (10 mg/kg,
maximal dose that could administered given limited solubility) (n = 3), TDB-imi6 (25 mg/kg) (n = 5), and vehicle control (n = 6). (b) Administration
of MTDB-imi6 leads to a decrease in lung viral load of
SARS-CoV-2 infected K18-hACE2 mice. No differences in lung viral load
between vehicle control and MTDB and TDB-imi6-treated mice were observed. Mean ± SD is shown; *p < 0.05; unpaired t test. (c) Western blot analysis
of phospho-p38 from lung extracts of transgenic K18-hACE2 mice treated
with three doses of 10 mg/kg of vehicle (V1, V2) or MTDB-imi6 (D1, D2) at 1 h before infection and 1 and 2 days postinfection
(n = 2).