A study on catalytic and non-catalytic sites of H5N1 and H1N1 neuraminidase as the target for chalcone inhibitors
| Autor: | Eko Aprilianto, Christophorus Fideluno Adhipandito, Evan Julian Candaya, Maywan Hariono, Habibah A. Wahab, Jasvidianto Chriza Kotta, Pandu Hariyono |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Chalcone
Oseltamivir Non-catalytic site genetic structures In silico Neuraminidase medicine.disease_cause behavioral disciplines and activities General Biochemistry Genetics and Molecular Biology Virus Article chemistry.chemical_compound medicine IC50 chemistry.chemical_classification biology Organic Chemistry H1N1 virus diseases H5N1 Influenza A virus subtype H5N1 Influenza Enzyme nervous system chemistry Biochemistry biology.protein psychological phenomena and processes |
| Zdroj: | Applied Biological Chemistry |
| ISSN: | 2468-0842 2468-0834 |
| Popis: | 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 IC50 of 27.63 µM and 28.11 µM, respectively, whereas compound 2b inhibits NAs with IC50 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink