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Volume 21, Issue 18
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

Neuraminidase enzyme plays a major role in the life cycle of influenza viruses. Targeting neuraminidases is a key strategy in preventing and treating influenza A and B spread by inhibiting the release of new viral particles from infected cells. Developing new neuraminidase inhibitors with enhanced efficacy and reduced risk of resistance is the ultimate of ongoing research.

Objective

In this study, we tried to shed light on molecules of natural origin that inhibit neuraminidase enzyme by utilizing different aspects of studies.

Methods

The work started by generating structure-based pharmacophore, later used for the virtual screening of electronic libraries constructed from chemical and natural compounds. Hits raised from virtual screening were subjected to molecular docking to assess and explain different modes of interactions with the neuraminidase enzyme. Drug likeness and ADME filters were applied to choose compounds that may be taken effectively by oral route with good gastrointestinal absorption and acceptable pharmacokinetics with respect to Lipinski and Ghose rules. The hits were also inspected for toxicity risks, including mutagenic, tumorigenic, irritant, and reproductive effects.

Results

7 features of the generated pharmacophore from the potent inhibitor Oselatamiver were the base for virtual screening. The results obtained by database screening highlighted 4 natural compounds listed in the COCONUT library (CNP 0125691 (Penicitrinol K), CNP0256196 (Frenolicin D), CNP 0138184, and CNP 0206296) as potential neuraminidase inhibitors. The compounds showed a similar interaction profile to Oseltamivir by molecular docking with high binding affinity. The key residue TYR 406 hydrogen bonded to Penicitrinol and Frenolicin D as well as to Oseltamevir. The 4 natural compounds exerted drug-like properties and promising pharmacokinetic characters. Toxicity risks estimations put Penicitrinol K and Frenolicin as devoted to mutagenic, tumorigenic, irritant and reproductive potentials. Penicitrinol K and Frenolicin are assigned for further and studies as promising neuraminidase inhibitors.

Conclusion

Penicitrinol K, and Frenolicin D are promising natural neuraminidase inhibitors, exhibiting favourable drug-like properties and low toxicity risks in addition to showing the pattern of interaction profiles with neuraminidase enzymes similar to the known drug Oseltamivir contributing to the development of effective antiviral therapies against influenza, suggesting further and evaluation.

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2024-11-08
2025-06-28

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Unlocking Neuraminidase Inhibitors: Insights from Natural Products through Pharmacophore Modeling, Virtual Screening, and Molecular Docking
Letters in Drug Design & Discovery 21, 4366 (2024); https://doi.org/10.2174/0115701808334140241107111104
/content/journals/lddd/10.2174/0115701808334140241107111104
/content/journals/lddd/10.2174/0115701808334140241107111104
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  • Article Type:     Research Article
Keyword(s): docking; drug likeness; enzymes; Neuraminidase; pharmacophore; virtual screening

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