MI-09
A SARS-CoV-2 3C-like protease inhibitor.
General information
MI-09 is a designed potent SARS-CoV-2 covalent 3C-like protease inhibitor. It displays efficacy in hACE2-mice and good toxicity profile and pharmacokinetic properties in rats (Qiao et al., 2021).
Synonyms
(1R,2S,5S)-6,6-dimethyl-N-((S)-1-oxo-3-((S)-2-oxopyrrolidin-3-yl)propan-2-yl)-3-(2-(4- (trifluoromethoxy) phenoxy) acetyl)-3-azabicyclo[3.1.0]hexane-2-carboxamide
C(F)(F)(F)OC1=CC=C(C=C1)OC(=O)N2[C@@H]([C@@H]3[C@H](C2)C3(C)C)C(=O)N([C@@H](C[C@H]4C(=O)N(CC4)[H])C(=O)[H])[H]
Supporting references
| Link | Tested on | Impact factor | Notes | Publication date |
|---|---|---|---|---|
|
SARS-CoV-2 Mpro inhibitors with antiviral activity in a transgenic mouse model
3CLpro Crystallization Biophysical assay Small molecule Enzyme assay Animal model In vitro Mechanism In silico |
in silico; crystallization; in vitro enzyme assay; in vitro biophysical assay; Vero E6, HPAEpiC, LO2, BEAS-2B, A549 and Huh7 cells (cytotoxicity); Vero E6 cells; Sprague-Dawley rats (pharmacokinetics and toxicity); hACE2 mice | 41.85 | The compound was computationally designed to covalently bind the SARS-CoV-2 3C-like protease active site. The binding was experimentally verified in vitro. MI-09 protected Vero E6 cells and HPAEpiC cells from SARS-CoV-2 infection with an EC50 of 0.86 μM and 1.2 nM, respectively. It displayed efficacy in Huh7 cells (two-digit nanomolar concentration), as well. The compound showed good pharmacokinetic properties, oral bioavailability, and low toxicity in rats. The efficacy of MI-09 against SARS-CoV-2 infection was tested on hACE2-mouse model. After a moderate viral challenge, the SARS-CoV-2 RNA levels in the treated mice were statistically significantly lower compared to control on day 3 post infection. The treatment ameliorated lung tissue damage and decreased the host’s immune response. |
Feb/18/2021 |
