TY  - JOUR
AU  - Ferjančić, Zorana
AU  - Bihelović, Filip
AU  - Vulović, Bojan
AU  - Matović, Radomir
AU  - Trmčić, Milena
AU  - Jankovic, Aleksandar
AU  - Pavlovic, Milos
AU  - Đurković, Filip T.
AU  - Prodanović, Radivoje
AU  - Djurdjevic Djelmas, Aleksandra
AU  - Kalicanin, Nevena
AU  - Zlatović, Mario
AU  - Sladić, Dušan
AU  - Vallet, Thomas
AU  - Vignuzzi, Marco
AU  - Saicic, Radomir N.
PY  - 2024
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/6475
AB  - We developed new iminosugar-based glycosidase inhibitors against SARS-CoV-2. Known drugs (miglustat, migalastat, miglitol, and swainsonine) were chosen as lead compounds to develop three classes of glycosidase inhibitors (α-glucosidase, α-galactosidase, and mannosidase). Molecular modelling of the lead compounds, synthesis of the compounds with the highest docking scores, enzyme inhibition tests, and in vitro antiviral assays afforded rationally designed inhibitors. Two highly active α-glucosidase inhibitors were discovered, where one of them is the most potent iminosugar-based anti-SARS-CoV-2 agent to date (EC90 = 1.94 µM in A549-ACE2 cells against Omicron BA.1 strain). However, galactosidase inhibitors did not exhibit antiviral activity, whereas mannosidase inhibitors were both active and cytotoxic. As our iminosugar-based drug candidates act by a host-directed mechanism, they should be more resilient to drug resistance. Moreover, this strategy could be extended to identify potential drug candidates for other viral infections.
PB  - Taylor and Francis Group
T2  - Journal of Enzyme Inhibition and Medicinal Chemistry
T1  - Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies
VL  - 39
IS  - 1
SP  - 2289007
DO  - 10.1080/14756366.2023.2289007
ER  - 

@article{
author = "Ferjančić, Zorana and Bihelović, Filip and Vulović, Bojan and Matović, Radomir and Trmčić, Milena and Jankovic, Aleksandar and Pavlovic, Milos and Đurković, Filip T. and Prodanović, Radivoje and Djurdjevic Djelmas, Aleksandra and Kalicanin, Nevena and Zlatović, Mario and Sladić, Dušan and Vallet, Thomas and Vignuzzi, Marco and Saicic, Radomir N.",
year = "2024",
abstract = "We developed new iminosugar-based glycosidase inhibitors against SARS-CoV-2. Known drugs (miglustat, migalastat, miglitol, and swainsonine) were chosen as lead compounds to develop three classes of glycosidase inhibitors (α-glucosidase, α-galactosidase, and mannosidase). Molecular modelling of the lead compounds, synthesis of the compounds with the highest docking scores, enzyme inhibition tests, and in vitro antiviral assays afforded rationally designed inhibitors. Two highly active α-glucosidase inhibitors were discovered, where one of them is the most potent iminosugar-based anti-SARS-CoV-2 agent to date (EC90 = 1.94 µM in A549-ACE2 cells against Omicron BA.1 strain). However, galactosidase inhibitors did not exhibit antiviral activity, whereas mannosidase inhibitors were both active and cytotoxic. As our iminosugar-based drug candidates act by a host-directed mechanism, they should be more resilient to drug resistance. Moreover, this strategy could be extended to identify potential drug candidates for other viral infections.",
publisher = "Taylor and Francis Group",
journal = "Journal of Enzyme Inhibition and Medicinal Chemistry",
title = "Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies",
volume = "39",
number = "1",
pages = "2289007",
doi = "10.1080/14756366.2023.2289007"
}

Ferjančić, Z., Bihelović, F., Vulović, B., Matović, R., Trmčić, M., Jankovic, A., Pavlovic, M., Đurković, F. T., Prodanović, R., Djurdjevic Djelmas, A., Kalicanin, N., Zlatović, M., Sladić, D., Vallet, T., Vignuzzi, M.,& Saicic, R. N.. (2024). Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies. in Journal of Enzyme Inhibition and Medicinal Chemistry
Taylor and Francis Group., 39(1), 2289007.
https://doi.org/10.1080/14756366.2023.2289007

Ferjančić Z, Bihelović F, Vulović B, Matović R, Trmčić M, Jankovic A, Pavlovic M, Đurković FT, Prodanović R, Djurdjevic Djelmas A, Kalicanin N, Zlatović M, Sladić D, Vallet T, Vignuzzi M, Saicic RN. Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies. in Journal of Enzyme Inhibition and Medicinal Chemistry. 2024;39(1):2289007.
doi:10.1080/14756366.2023.2289007 .

Ferjančić, Zorana, Bihelović, Filip, Vulović, Bojan, Matović, Radomir, Trmčić, Milena, Jankovic, Aleksandar, Pavlovic, Milos, Đurković, Filip T., Prodanović, Radivoje, Djurdjevic Djelmas, Aleksandra, Kalicanin, Nevena, Zlatović, Mario, Sladić, Dušan, Vallet, Thomas, Vignuzzi, Marco, Saicic, Radomir N., "Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies" in Journal of Enzyme Inhibition and Medicinal Chemistry, 39, no. 1 (2024):2289007,
https://doi.org/10.1080/14756366.2023.2289007 . .