Ibuprofen as a template molecule for drug design against Ebola virus

Paessler, Slobodan; Huang, Cheng; Senćanski, Milan; Veljković, Nevena; Perovic, Vladimir; Glišić, Sanja; Veljkovic, Veljjko

doi:10.2741/4627

Cited by 20 publications

(8 citation statements)

References 11 publications

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“…Previously, the EIIP/AQVN criterion has been proven to be an efficient filter in virtual screening of molecular libraries for candidate inhibitors of HIV and Ebola virus infection (Tintori et al, 2007; Veljkovic et al, 2015a,b). Using this approach, ibuprofen was selected as an inhibitor of the Ebola virus infection, and this prediction was later experimentally confirmed (Zhao et al, 2016; Paessler et al, 2018. )…”

Section: Discussionmentioning

confidence: 96%

Virtual Screen for Repurposing of Drugs for Candidate Influenza a M2 Ion-Channel Inhibitors

Radošević

Senćanski

Perović

et al. 2019

Front. Cell. Infect. Microbiol.

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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-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.

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Section: Discussionmentioning

confidence: 96%

Virtual Screen for Repurposing of Drugs for Candidate Influenza a M2 Ion-Channel Inhibitors

Radošević

Senćanski

Perović

et al. 2019

Front. Cell. Infect. Microbiol.

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“…The WHO has indicated that there is no evidence to confirm an aggravation of COVID-19 infection with the administration of NSAIDs [30,31]. In fact, it has been reported that some NSAIDs could have some type of activity against viruses such as VZV [32], HCMV [32], HSV-1 [33], influenza virus A⁄ H1N1 subtype [34,35], VSV [36,37], EBOLA [38,39], HIV [40], JEV [41], CHIKV [42], SARS-CoV-1 [43], and recently against SARS-CoV-2 [35,44,45]. Additionally, many studies have been carried out that propose various targets for blocking virus recognition, importation and replication processes through the use of reused drugs, immunotherapies, interference strategies and various inhibitory compounds [46].…”

Section: Introductionmentioning

confidence: 99%

Can Non-steroidal Anti-inflammatory Drugs Affect the Interaction Between Receptor Binding Domain of SARS-COV-2 Spike and the Human ACE2 Receptor? A Computational Biophysical Study

et al. 2020

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“…Antiinflammatory compounds, including nonsteroidal antiinflammatory drugs (NSAIDs), can control fever and other aspects of the “cytokine storm” that several different viruses induce. Ibuprofen has been suggested to control Ebola symptoms . NSAIDs can also improve survival in cancers, for example in patients with activating mutations in PIK3CA, which are very common in head and neck cancers.…”

Section: Finding New Uses For Approved Drugsmentioning

confidence: 99%

Repurposing approved drugs on the pathway to novel therapies

Schein

2019

Medicinal Research Reviews

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The time and cost of developing new drugs have led many groups to limit their search for therapeutics to compounds that have previously been approved for human use. Many “repurposed” drugs, such as derivatives of thalidomide, antibiotics, and antivirals have had clinical success in treatment areas well beyond their original approved use. These include applications in treating antibiotic‐resistant organisms, viruses, cancers and to prevent burn scarring. The major theoretical justification for reusing approved drugs is that they have known modes of action and controllable side effects. Coadministering antibiotics with inhibitors of bacterial toxins or enzymes that mediate multidrug resistance can greatly enhance their activity. Drugs that control host cell pathways, including inflammation, tumor necrosis factor, interferons, and autophagy, can reduce the “cytokine storm” response to injury, control infection, and aid in cancer therapy. An active compound, even if previously approved for human use, will be a poor clinical candidate if it lacks specificity for the new target, has poor solubility or can cause serious side effects. Synergistic combinations can reduce the dosages of the individual components to lower reactivity. Preclinical analysis should take into account that severely ill patients with comorbidities will be more sensitive to side effects than healthy trial subjects. Once an active, approved drug has been identified, collaboration with medicinal chemists can aid in finding derivatives with better physicochemical properties, specificity, and efficacy, to provide novel therapies for cancers, emerging and rare diseases.

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Ibuprofen as a template molecule for drug design against Ebola virus

Cited by 20 publications

References 11 publications

Virtual Screen for Repurposing of Drugs for Candidate Influenza a M2 Ion-Channel Inhibitors

Virtual Screen for Repurposing of Drugs for Candidate Influenza a M2 Ion-Channel Inhibitors

Can Non-steroidal Anti-inflammatory Drugs Affect the Interaction Between Receptor Binding Domain of SARS-COV-2 Spike and the Human ACE2 Receptor? A Computational Biophysical Study

Repurposing approved drugs on the pathway to novel therapies

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