A study on catalytic and non-catalytic sites of H5N1 and H1N1 neuraminidase as the target for chalcone inhibitors.

UNLABELLED

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 ( and ) have the potential for future NA inhibitor development. Compound inhibits H5N1 NA and H1N1 NA with IC of 27.63 µM and 28.11 µM, respectively, whereas compound inhibits NAs with IC of 87.54 µM and 73.17 µM for H5N1 and H1N1, respectively. The in silico drug-like likeness prediction reveals that is 62% better than (58%) in meeting the criteria. The results suggested that and have potencies to be developed as non-competitive inhibitors of neuraminidase for the future development of anti-influenza drugs.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s13765-021-00639-w.