Valentina Gentili, Silvia Beltrami, Doretta Cuffaro, Giorgia Cianci, Gloria Maini, Roberta Rizzo, Marco Macchia, Armando Rossello, Daria Bortolotti, Elisa Nuti
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JG26 attenuates ADAM17 metalloproteinase-mediated ACE2 receptor processing and SARS-CoV-2 infection in vitro
Background
ADAM17 is a metalloprotease implicated in the proteolysis of angiotensin-converting enzyme 2 (ACE2), known to play a critical role in the entry and spread of SARS-CoV-2. In this context, ADAM17 results as a potential novel target for controlling SARS-CoV-2 infection.
Methods
In this study, we investigated the impact on ACE2 surface expression and the antiviral efficacy against SARS-CoV-2 infection of the selective ADAM17 inhibitor JG26 and its dimeric (compound 1) and glycoconjugate (compound 2) derivatives using Calu-3 human lung cells.
Results
None of the compounds exhibited cytotoxic effects on Calu-3 cells up to a concentration of 25 µM. Treatment with JG26 resulted in partial inhibition of both ACE2 receptor shedding and SARS-CoV-2 infection, followed by compound 1.
Conclusion
JG26, an ADAM17 inhibitor, demonstrated promising antiviral activity against SARS-CoV-2 infection, likely attributed to reduced sACE2 availability, thus limiting viral dissemination.
期刊介绍：
Pharmacological Reports publishes articles concerning all aspects of pharmacology, dealing with the action of drugs at a cellular and molecular level, and papers on the relationship between molecular structure and biological activity as well as reports on compounds with well-defined chemical structures.
Pharmacological Reports is an open forum to disseminate recent developments in: pharmacology, behavioural brain research, evidence-based complementary biochemical pharmacology, medicinal chemistry and biochemistry, drug discovery, neuro-psychopharmacology and biological psychiatry, neuroscience and neuropharmacology, cellular and molecular neuroscience, molecular biology, cell biology, toxicology.
Studies of plant extracts are not suitable for Pharmacological Reports.
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