| Title: | In silico determination of novel SARS-CoV-2 envelope protein ion channel inhibitors |
|---|
| Authors: | ID Kobe, Nina (Author)
ID Dreisewerd, Lennart (Author)
ID Pavlin, Matic (Author)
ID Kogovšek, Polona (Author)
ID Podlipnik, Črtomir (Author)
ID Grošelj, Uroš (Author)
ID Lukšič, Miha (Author) |
|---|
| Files: |  URL - Source URL, visit https://www.csbj.org/article/S2001-0370(25)00255-7/fulltext
 PDF - Presentation file, download (1,82 MB)
MD5: 2E636090A08B5177D125256F0E5B7280
|
|---|
| Language: | English |
|---|
| Typology: | 1.01 - Original Scientific Article |
|---|
| Organization: |  NIB - National Institute of Biology
|
|---|
| Abstract: | 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. |
|---|
| Keywords: | SARS-CoV-2 envelope protein, viroporin, ion channel, channel blockers, molecular dynamics simulations, free energy calculations, drug discovery |
|---|
| Publication status: | Published |
|---|
| Publication version: | Version of Record |
|---|
| Publication date: | 26.06.2025 |
|---|
| Year of publishing: | 2025 |
|---|
| Number of pages: | str. 2823-2831 |
|---|
| Numbering: | Vol. 27 |
|---|
| PID: | 20.500.12556/DiRROS-23494  |
|---|
| UDC: | 577 |
|---|
| ISSN on article: | 2001-0370 |
|---|
| DOI: | 10.1016/j.csbj.2025.06.036 |
|---|
| COBISS.SI-ID: | 241440259 |
|---|
| Note: | Nasl. z nasl. zaslona;
Soavtorji: Lennart Dreisewerd, Matic Pavlin, Polona Kogovšek, Črtomir Podlipnik, Uroš Grošelj, Miha Lukšič;
Opis vira z dne 4. 7. 2025;
|
|---|
| Publication date in DiRROS: | 05.09.2025 |
|---|
| Views: | 323 |
|---|
| Downloads: | 129 |
|---|
| Metadata: |    |
|---|
|
:
|
Copy citation |
|---|
| | | | Share: |  |
|---|
Hover the mouse pointer over a document title to show the abstract or click
on the title to get all document metadata. |
