MI-30
A SARS-CoV-2 3C-like protease inhibitor.
General information
MI-30 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
(1S,3aR,6aS)-2-(2-(2,4-dichlorophenoxy)acetyl)-N-((S)-1-oxo-3-((S)-2-oxopyrrolidin-3- yl)propan-2-yl)octahydrocyclopenta[c]pyrrole-1-carboxamide
C1(=CC=C(C(=C1)Cl)OC(=O)N2[C@@H]([C@@H]3[C@H](C2)CCC3)C(=O)N([C@@H](C[C@H]4C(=O)N(CC4)[H])C(=O)[H])[H])Cl
Supporting references
| Link | Tested on | Impact factor | Notes | Publication date |
|---|---|---|---|---|
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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-30 protected Vero E6 cells and HPAEpiC cells from SARS-CoV-2 infection with an EC50 of 0.54 μM and 1.1 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-30 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 |
