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The inhibitory effect of sodium baicalin on oseltamivir-resistant influenza A virus via reduction of neuraminidase activity
- Source :
- Archives of Pharmacal Research. 41:664-676
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- Baicalin was identified as a neuraminidase (NA) inhibitor displaying anti-influenza A virus (IAV) activity. However, its poor solubility in saline has limited its use in the clinic. We generated sodium baicalin and showed that it exhibited greatly increased solubility in saline. Its efficacy against oseltamivir-resistant mutant A/FM/1/47-H275Y (H1N1-H275Y) was evaluated in vitro and in vivo. Results showed that 10 μM of sodium baicalin inhibited A/FM/1/47 (H1N1), A/Beijing/32/92 (H3N2) and H1N1-H275Y in MDCK cells in a dose-dependent manner, with inhibitory rates of 83.9, 75.9 and 47.7%, respectively. Intravenous administration of sodium baicalin at 100 mg/kg/d enabled the survival of 20% of H1N1-H275Y-infected mice. The treatment alleviated body weight loss and lung injury. Moreover, sodium baicalin exerted a clear inhibitory effect on NAs. The IC50 values of sodium baicalin against H1N1-H275Y and cells-expressing A/Anhui/1/2013-R294K (H7N9-R294K) NA protein (N9-R294K) were 214.4 μM and 216.3 μM. Direct interactions between sodium baicalin and NA were observed, and we simulated the interactions of sodium baicalin with N9-R294K and N9 near the active sites of OC-N9-R294K and OC-N9. The residues responsible for the sodium baicalin-N9-R294K and sodium baicalin-N9 interactions were the same, confirming that sodium baicalin exerts effects on wild-type and oseltamivir-resistant viral strains.
- Subjects :
- Male
0301 basic medicine
Scutellaria
medicine.medical_treatment
Sodium
030106 microbiology
Neuraminidase
chemistry.chemical_element
CHO Cells
Pharmacology
Lung injury
Virus Replication
medicine.disease_cause
Antiviral Agents
Madin Darby Canine Kidney Cells
Inhibitory Concentration 50
Mice
Viral Proteins
03 medical and health sciences
chemistry.chemical_compound
Cricetulus
Dogs
Oseltamivir
In vivo
Drug Resistance, Viral
Influenza, Human
Drug Discovery
medicine
Influenza A virus
Animals
Humans
Enzyme Inhibitors
Saline
Flavonoids
Mice, Inbred ICR
biology
Organic Chemistry
In vitro
Disease Models, Animal
030104 developmental biology
chemistry
biology.protein
Molecular Medicine
Administration, Intravenous
Baicalin
Subjects
Details
- ISSN :
- 19763786 and 02536269
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Archives of Pharmacal Research
- Accession number :
- edsair.doi.dedup.....e3ea12616aee1d1f9dfb68848ba67c64