2. Academic Validation
  3. JG26 attenuates ADAM17 metalloproteinase-mediated ACE2 receptor processing and SARS-CoV-2 infection in vitro

JG26 attenuates ADAM17 metalloproteinase-mediated ACE2 receptor processing and SARS-CoV-2 infection in vitro

  • Pharmacol Rep. 2025 Feb;77(1):260-273. doi: 10.1007/s43440-024-00650-0.
Valentina Gentili # 1,  Silvia Beltrami # 1,  Doretta Cuffaro 2,  Giorgia Cianci 1,  Gloria Maini 1,  Roberta Rizzo 1 3,  Marco Macchia 2,  Armando Rossello 2,  Daria Bortolotti # 4,  Elisa Nuti # 5
Affiliations

Affiliations

  • 1 Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari 46, Ferrara, 44121, Italy.
  • 2 Department of Pharmacy, University of Pisa, Via Bonanno 6, Pisa, 56126, Italy.
  • 3 Clinical Research Center, LTTA, University of Ferrara, Ferrara, Italy.
  • 4 Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari 46, Ferrara, 44121, Italy. brtdra@unife.it.
  • 5 Department of Pharmacy, University of Pisa, Via Bonanno 6, Pisa, 56126, Italy. elisa.nuti@unipi.it.
  • # Contributed equally.
PMID: 39292373 DOI: 10.1007/s43440-024-00650-0
Abstract

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.

Keywords

ADAM17; Antiviral activity; Arylsulfonamido-based hydroxamic acid; SARS-CoV-2; sACE2.

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