Exposure of human intestinal epithelial cells and primary human hepatocytes to trypsin-like serine protease inhibitors with potential antiviral effect.
J Enzyme Inhib Med Chem
; 36(1): 659-668, 2021 Dec.
Article
in English
| MEDLINE | ID: covidwho-1109085
ABSTRACT
Human intestinal epithelial cell line-6 (HIEC-6) cells and primary human hepatocytes (PHHs) were treated with 3-amidinophenylalanine-derived inhibitors of trypsin-like serine proteases for 24 hours. It was proven that treatment with MI-1900 and MI-1907 was tolerated up to 50 µM in HIEC-6. These inhibitors did not cause elevations in extracellular H2O2 levels and in the concentrations of interleukin (IL)-6 and IL-8 and did not alter occludin distribution in HIEC-6. It was also found that MI-1900 and MI-1907 up to 50 µM did not affect cell viability, IL-6 and IL-8 and occludin levels of PHH. Based on our findings, these inhibitors could be safely applicable at 50 µM in HIEC-6 and in PHH; however, redox status was disturbed in case of PHH. Moreover, it has recently been demonstrated that MI-1900 prevents the replication and spread of the new SARS-CoV-2 in infected Calu-3 cells, most-likely via an inhibition of the membrane-bound host protease TMPRSS2.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Phenylalanine
/
Protease Inhibitors
/
Serine Endopeptidases
/
Hepatocytes
/
Epithelial Cells
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
J Enzyme Inhib Med Chem
Journal subject:
Biochemistry
/
Chemistry
Year:
2021
Document Type:
Article
Affiliation country:
14756366.2021.1886093
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