20.500.12556/DiRROS-23494 In silico determination of novel SARS-CoV-2 envelope protein ion channel inhibitors The SARS-CoV-2 envelope protein (2-EPRO), a viroporin crucial for viral pathogenesis, is a promising target for antiviral drug development as it is highly conserved and functionally important. Although it is a promising therapeutic target for the treatment of COVID-19, it has often been overlooked in previous studies. In this study, a high-throughput virtual screening of nearly one billion compounds was performed, followed by rigorous filtering and re-docking. Eight best-scoring and chemically versatile lead candidates were identified. In molecular dynamics simulations, three of these ligands showed stable protein-ligand complexes occupying the 2-EPRO channel pore. Among these, ZINC001799167680 (L3) and ZINC001081252239 (L2) exhibited the strongest binding a˙inity, with key interactions at residues ASN15, THR11 and GLU8 identified by Molecular Mechanics Poisson-Boltzmann Surface Area analysis. All ligands were compared with the known inhibitor rimantadine and showed stronger binding to the protein. These in silico results highlight the potential of focusing on the 2-EPRO ion channel in the development of novel COVID-19 therapeutics and pave the way for further in vitro and in vivo studies. SARS-CoV-2 envelope protein viroporin ion channel channel blockers molecular dynamics simulations free energy calculations drug discovery E protein SARS-CoV-2 viroporin ionski kanal molekulska dinamika odkrivanje zdravil true false true Angleški jezik Slovenski jezik Neznano 2025-09-05 09:54:22 2025-09-05 09:54:22 2025-10-24 03:54:26 0000-00-00 00:00:00 2025 0 0 Nasl. z nasl. zaslona; Soavtorji: Lennart Dreisewerd, Matic Pavlin, Polona Kogovšek, Črtomir Podlipnik, Uroš Grošelj, Miha Lukšič; Opis vira z dne 4. 7. 2025; str. 2823-2831 Vol. 27 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2025-06-26 577 2001-0370 10.1016/j.csbj.2025.06.036 241440259 https://www.csbj.org/article/S2001-0370(25)00255-7/fulltext 1 8ba2d484-8a2d-11f0-9bb7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=34751 RAZ_Kobe_Nina_2025.pdf RAZ_Kobe_Nina_2025.pdf 1 2E636090A08B5177D125256F0E5B7280 fcf5cbec2c199c5f9cd60431197e37827e805e1fad711e8405e5096667309d67 2c479260-8a2e-11f0-9bb7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=34752 Nacionalni inštitut za biologijo 0 0 0