3rd International Conference on Chemo and BioInformatics, Kragujevac, September 25-26. 2025. (pp. 569-572)
АУТОР(И) / AUTHOR(S): Anja Kolarič, Vid Ravnik, Marko Jukič, Urban Bren
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DOI: 10.46793/ICCBIKG25.569K
САЖЕТАК / ABSTRACT:
The furin protease plays a crucial role in the activation of pathogenic proteins, including the SARS-CoV-2 spike protein, which is a crucial step in virus binding and the subsequent viral entry into human cells. To identify potential furin inhibitors, we employed a virtual screening strategy using the MADE approach, which is based on water-mediated ligand– furin interactions. A compound library was compiled based on the hydrogen bond donor and acceptor profiles of known furin inhibitors, and molecular docking was performed using 21 conserved water molecules identified by MADE. The predicted binding modes of the hit compounds with novel scaffolds showed similar interaction patterns to those of the known furin inhibitors, with key residues interacting with the ligands through both direct and water-mediated hydrogen bonding. These results suggest that the identified compounds represent promising starting points for the development of small molecule furin inhibitors with potential applications in the treatment of furin-dependent diseases and viral infections.
КЉУЧНЕ РЕЧИ / KEYWORDS:
furin, water-aware molecular docking, antiviral drug design
ПРОЈЕКАТ / ACKNOWLEDGEMENT:
This work was supported by the Slovenian Research and Innovation Agency (ARIS) program and project grants J1-2471, P2-0046, L2-3175, J4-4633, J1-4398, L2-4430, J3-4498, J7-4638, J1-4414, J3-4497, P2-0438, IO-E015, J1-50034, J7-50043, Z1-50021, and P10403.
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