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A study on catalytic and non-catalytic sites of H5N1 and H1N1 neuraminidase as the target for chalcone inhibitors
The H1N1 pandemic in 2009 and the H5N1 outbreak in 2005 have shocked the world as millions of people were infected and hundreds of thousands died due to the infections by the influenza virus. Oseltamivir, the most common drug to block the viral life cycle by inhibiting neuraminidase (NA) enzyme, has...
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Published in: | Applied biological chemistry 2021, 64(5), , pp.1-17 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | The H1N1 pandemic in 2009 and the H5N1 outbreak in 2005 have shocked the world as millions of people were infected and hundreds of thousands died due to the infections by the influenza virus. Oseltamivir, the most common drug to block the viral life cycle by inhibiting neuraminidase (NA) enzyme, has been less effective in some resistant cases due to the virus mutation. Presently, the binding of 10 chalcone derivatives towards H5N1 and H1N1 NAs in the non-catalytic and catalytic sites was studied using molecular docking. The in silico study was also conducted for its drug-like likeness such as Lipinski Rule, mutagenicity, toxicity and pharmacokinetic profiles. The result demonstrates that two chalcones (
1c
and
2b
) have the potential for future NA inhibitor development. Compound
1c
inhibits H5N1 NA and H1N1 NA with IC
50
of 27.63 µM and 28.11 µM, respectively, whereas compound
2b
inhibits NAs with IC
50
of 87.54 µM and 73.17 µM for H5N1 and H1N1, respectively. The in silico drug-like likeness prediction reveals that
1c
is 62% better than
2b
(58%) in meeting the criteria. The results suggested that
1c
and
2b
have potencies to be developed as non-competitive inhibitors of neuraminidase for the future development of anti-influenza drugs. |
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ISSN: | 2468-0834 2468-0842 |
DOI: | 10.1186/s13765-021-00639-w |