Characterization of the symmetrical benzimidazole twin drug TL1228: the role as viral entry inhibitor for fighting COVID-19
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is reliably one of the largest pandemics the world has suffered in recent years. In the search for non-biological antivirals, special emphasis was placed on drug repurposing to accelerate the clinical implementation of effective drugs.The life cycle of the virus has been extensively investigated and many human targets have been identified, such as the molecular chaperone GRP78, representing a host auxiliary factor for SARS-CoV-2 entry. Here we report the inhibitor capacity of TL1228, a small molecule discovered through an in silico screening approach, which could interfere with the interaction of SARS-CoV-2 and its target cells, blocking the recognition of the GRP78 cellular receptor by the viral Spike protein. TL1228 showed in vitro the ability to reduce significantly both pseudoviral and authentic viral activity even through the reduction of GRP78/ACE2 transcript levels. Importantly, TL1228 acts in modulating expression levels of innate immunity and as inflammation markers.
Authors
- Claudia Valeria Campos de Souza
- Federica Sangiuolo (ORCID: https://orcid.org/0000-0002-6227-4248)
- Michela Murdocca (ORCID: https://orcid.org/0000-0001-8088-3664)
- Annie Mayence (ORCID: https://orcid.org/0000-0003-2509-7593)
- Andrea Duranti (ORCID: https://orcid.org/0000-0002-7531-4472)
- Bruno Brandimarte
- Jean Jacques Vanden Eynde (ORCID: https://orcid.org/0000-0003-4770-4104)
- Lino Di Rienzo Businco (ORCID: https://orcid.org/0009-0003-1546-4836)
- Claudia De Masi (ORCID: https://orcid.org/0000-0001-9677-9554)
- Donatella Amatore (ORCID: https://orcid.org/0000-0001-5701-9683)
- Andrea Latini (ORCID: https://orcid.org/0000-0002-5350-7361)
- Tien L. Huang
- Osvaldo A. Santos‐Filho (ORCID: https://orcid.org/0000-0001-7407-158X)
- Giuseppe Novelli (ORCID: https://orcid.org/0000-0002-7781-602X)
- Florigio Lista (ORCID: https://orcid.org/0000-0002-9495-2656)
- Giorgia Grilli (ORCID: https://orcid.org/0009-0009-4993-6823)
- Riccardo De Santis (ORCID: https://orcid.org/0000-0002-2097-6663)
- Edivaldo dos Santos Rodrigues
- Rossella Schipani
Institutions
- University of Rome Tor Vergata (IT)
- Universidade Federal do Rio de Janeiro (BR)
- University of Mons (BE)
- Xavier University of Louisiana (US)
- University of Urbino (IT)
- Czech Academy of Sciences, Institute of Biophysics (CZ)
- Ministry of Defence (IT)
- Institute of Sports Medicine and Science (JP)
- Sapienza University of Rome (IT)
Publication Details
- Journal
- Biology Direct
- Published
- 2024-10-16
- DOI
- https://doi.org/10.1186/s13062-024-00523-9
- Citations
- 1
- Primary Topic
- Synthesis and biological activity
- Type
- article
- Field-Weighted Citation Impact
- 0.25
Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior