Virtual Screen for Repurposing of Drugs for Candidate Influenza a M2 Ion-Channel Inhibitors
Autori
Radošević, Draginja![](/themes/MirageVinar/images/orcid.png)
Senćanski, Milan V.
![](/themes/MirageVinar/images/orcid.png)
Perović, Vladimir R.
![](/themes/MirageVinar/images/orcid.png)
Veljković, Nevena V.
![](/themes/MirageVinar/images/orcid.png)
Prljić, Jelena
![](/themes/MirageVinar/images/orcid.png)
Veljković, Veljko
![](/themes/MirageVinar/images/orcid.png)
Mantlo, Emily
Bukreyeva, Natalya
Paessler, Slobodan
Glišić, Sanja
![](/themes/MirageVinar/images/orcid.png)
Članak u časopisu (Objavljena verzija)
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© 2019 Radosevic, Sencanski, Perovic, Veljkovic, Prljic, Veljkovic, Mantlo, Bukreyeva, Paessler and Glisic
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Influenza A virus (IAV) matrix protein 2 (M2), an ion channel, is crucial for virus infection, and therefore, an important anti-influenza drug target. Adamantanes, also known as M2 channel blockers, are one of the two classes of Food and Drug Administration-approved anti-influenza drugs, although their use was discontinued due to prevalent drug resistance. Fast emergence of resistance to current anti-influenza drugs have raised an urgent need for developing new anti-influenza drugs against resistant forms of circulating viruses. Here we propose a simple theoretical criterion for fast virtual screening of molecular libraries for candidate anti-influenza ion channel inhibitors both for wild type and adamantane-resistant influenza A viruses. After in silico screening of drug space using the EIIP/AQVN filter and further filtering of drugs by ligand based virtual screening and molecular docking we propose the best candidate drugs as potential dual inhibitors of wild type and adamantane-resi...stant influenza A viruses. Finally, guanethidine, the best ranked drug selected from ligand-based virtual screening, was experimentally tested. The experimental results show measurable anti-influenza activity of guanethidine in cell culture. © 2019 Radosevic, Sencanski, Perovic, Veljkovic, Prljic, Veljkovic, Mantlo, Bukreyeva, Paessler and Glisic.
Ključne reči:
influenza A / IAV matrix protein 2 / drug repurposing / virtual screening / drug resistanceIzvor:
Frontiers in Cellular and Infection Microbiology, 2019, 9, 67-Finansiranje / projekti:
- Primena EIIP/ISM bioinformatičke platforme u otkrivanju novih terapeutskih targeta i potencijalnih terapeutskih molekula (RS-MESTD-Basic Research (BR or ON)-173001)
DOI: 10.3389/fcimb.2019.00067
ISSN: 2235-2988
PubMed: 30972303
WoS: 000462545200002
Scopus: 2-s2.0-85064721873
URI
https://www.frontiersin.org/article/10.3389/fcimb.2019.00067/fullhttps://vinar.vin.bg.ac.rs/handle/123456789/8163
Kolekcije
Institucija/grupa
VinčaTY - JOUR AU - Radošević, Draginja AU - Senćanski, Milan V. AU - Perović, Vladimir R. AU - Veljković, Nevena V. AU - Prljić, Jelena AU - Veljković, Veljko AU - Mantlo, Emily AU - Bukreyeva, Natalya AU - Paessler, Slobodan AU - Glišić, Sanja PY - 2019 UR - https://www.frontiersin.org/article/10.3389/fcimb.2019.00067/full UR - https://vinar.vin.bg.ac.rs/handle/123456789/8163 AB - Influenza A virus (IAV) matrix protein 2 (M2), an ion channel, is crucial for virus infection, and therefore, an important anti-influenza drug target. Adamantanes, also known as M2 channel blockers, are one of the two classes of Food and Drug Administration-approved anti-influenza drugs, although their use was discontinued due to prevalent drug resistance. Fast emergence of resistance to current anti-influenza drugs have raised an urgent need for developing new anti-influenza drugs against resistant forms of circulating viruses. Here we propose a simple theoretical criterion for fast virtual screening of molecular libraries for candidate anti-influenza ion channel inhibitors both for wild type and adamantane-resistant influenza A viruses. After in silico screening of drug space using the EIIP/AQVN filter and further filtering of drugs by ligand based virtual screening and molecular docking we propose the best candidate drugs as potential dual inhibitors of wild type and adamantane-resistant influenza A viruses. Finally, guanethidine, the best ranked drug selected from ligand-based virtual screening, was experimentally tested. The experimental results show measurable anti-influenza activity of guanethidine in cell culture. © 2019 Radosevic, Sencanski, Perovic, Veljkovic, Prljic, Veljkovic, Mantlo, Bukreyeva, Paessler and Glisic. T2 - Frontiers in Cellular and Infection Microbiology T1 - Virtual Screen for Repurposing of Drugs for Candidate Influenza a M2 Ion-Channel Inhibitors VL - 9 SP - 67 DO - 10.3389/fcimb.2019.00067 ER -
@article{ author = "Radošević, Draginja and Senćanski, Milan V. and Perović, Vladimir R. and Veljković, Nevena V. and Prljić, Jelena and Veljković, Veljko and Mantlo, Emily and Bukreyeva, Natalya and Paessler, Slobodan and Glišić, Sanja", year = "2019", abstract = "Influenza A virus (IAV) matrix protein 2 (M2), an ion channel, is crucial for virus infection, and therefore, an important anti-influenza drug target. Adamantanes, also known as M2 channel blockers, are one of the two classes of Food and Drug Administration-approved anti-influenza drugs, although their use was discontinued due to prevalent drug resistance. Fast emergence of resistance to current anti-influenza drugs have raised an urgent need for developing new anti-influenza drugs against resistant forms of circulating viruses. Here we propose a simple theoretical criterion for fast virtual screening of molecular libraries for candidate anti-influenza ion channel inhibitors both for wild type and adamantane-resistant influenza A viruses. After in silico screening of drug space using the EIIP/AQVN filter and further filtering of drugs by ligand based virtual screening and molecular docking we propose the best candidate drugs as potential dual inhibitors of wild type and adamantane-resistant influenza A viruses. Finally, guanethidine, the best ranked drug selected from ligand-based virtual screening, was experimentally tested. The experimental results show measurable anti-influenza activity of guanethidine in cell culture. © 2019 Radosevic, Sencanski, Perovic, Veljkovic, Prljic, Veljkovic, Mantlo, Bukreyeva, Paessler and Glisic.", journal = "Frontiers in Cellular and Infection Microbiology", title = "Virtual Screen for Repurposing of Drugs for Candidate Influenza a M2 Ion-Channel Inhibitors", volume = "9", pages = "67", doi = "10.3389/fcimb.2019.00067" }
Radošević, D., Senćanski, M. V., Perović, V. R., Veljković, N. V., Prljić, J., Veljković, V., Mantlo, E., Bukreyeva, N., Paessler, S.,& Glišić, S.. (2019). Virtual Screen for Repurposing of Drugs for Candidate Influenza a M2 Ion-Channel Inhibitors. in Frontiers in Cellular and Infection Microbiology, 9, 67. https://doi.org/10.3389/fcimb.2019.00067
Radošević D, Senćanski MV, Perović VR, Veljković NV, Prljić J, Veljković V, Mantlo E, Bukreyeva N, Paessler S, Glišić S. Virtual Screen for Repurposing of Drugs for Candidate Influenza a M2 Ion-Channel Inhibitors. in Frontiers in Cellular and Infection Microbiology. 2019;9:67. doi:10.3389/fcimb.2019.00067 .
Radošević, Draginja, Senćanski, Milan V., Perović, Vladimir R., Veljković, Nevena V., Prljić, Jelena, Veljković, Veljko, Mantlo, Emily, Bukreyeva, Natalya, Paessler, Slobodan, Glišić, Sanja, "Virtual Screen for Repurposing of Drugs for Candidate Influenza a M2 Ion-Channel Inhibitors" in Frontiers in Cellular and Infection Microbiology, 9 (2019):67, https://doi.org/10.3389/fcimb.2019.00067 . .