Virtual Screen for Repurposing of Drugs for Candidate Influenza a M2 Ion-Channel Inhibitors
Authors
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)
Article (Published version)
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© 2019 Radosevic, Sencanski, Perovic, Veljkovic, Prljic, Veljkovic, Mantlo, Bukreyeva, Paessler and Glisic
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Show full item recordAbstract
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.
Keywords:
influenza A / IAV matrix protein 2 / drug repurposing / virtual screening / drug resistanceSource:
Frontiers in Cellular and Infection Microbiology, 2019, 9, 67-Funding / projects:
- Application of the EIIP/ISM bioinformatics platform in discovery of novel therapeutic targets and potential therapeutic molecules (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
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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 . .