Virtual Screen for Repurposing of Drugs for Candidate Influenza a M2 Ion-Channel Inhibitors
Senćanski, Milan V.
Perović, Vladimir R.
Veljković, Nevena V.
Article (Published version)
© 2019 Radosevic, Sencanski, Perovic, Veljkovic, Prljic, Veljkovic, Mantlo, Bukreyeva, Paessler and Glisic
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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 resistance
Source:Frontiers in Cellular and Infection Microbiology, 2019, 9, MAR
- Application of the EIIP/ISM bioinformatics platform in discovery of novel therapeutic targets and potential therapeutic molecules (RS-173001)
ISSN: 2235-2988 (print)