ABSTRACT
Influenza remains one of the most widespread infections, causing an annual illness in adults and children. Therefore, the search for new antiviral drugs is one of the priorities of practical health care. Eight isorhamnetin glycosides were purified from Persicaria species, characterized by nuclear magnetic resonance spectroscopy and mass spectrometry and then evaluated as potential agents against influenza virus. A comprehensive in vitro and in vivo assessment of the compounds revealed that compound 5 displayed the most potent inhibitory activity with an EC50 value of 1.2-1.3 µM, better than standard drugs (isorhamnetin 28.0-56.0 µM and oseltamivir 1.3-9.1 µM). Molecular docking results also revealed that compound 5 has the lowest binding energy (-10.7 kcal/mol) among the tested compounds and isorhamnetin (-8.1 kcal/mol). The ability of the isorhamnetin glycosides to suppress the reproduction of the influenza virus was studied on a model of a cell culture and chicken embryos. The ability of active compounds to influence the structure of the virion, as well as the activity of hemagglutinin and neuraminidase, has been demonstrated. Compound 1, 5, and 6 demonstrated the most effective inhibition of virus replication for all tested viruses. Molecular dynamics simulation techniques were run for 100 ns for compound 5 with two protein receptors Hem (1RUY) and Neu (3BEQ). These results revealed that the Hem-complex system acquired a relatively more stable conformation and even better descriptors than the other Neu-complex studied systems, suggesting that it can be an effective inhibiting drug toward hemagglutinin than neuraminidase inhibition. Based on the reported results, compound 5 can be a good candidate to be evaluated for effectiveness in preclinical testing.
ABSTRACT
The use of the nanocapsulated adjuvant Sapomax increased the expression of innate immunity genes (H2Q10, Ddx58, Tyk2, Tlr3, Tlr7, and TNF) responsible for the primary recognition of influenza virus, i.e., those belonging to the RLR and TLR families; genes involved in stimulating the production of type I and III IFN and pro-inflammatory cytokines; and Th1 and Th2 cellular immunity genes (Ccr4, Ccr5, IFNγ, IL-2, IL-4, and IL-10) responsible for triggering regulatory immune mechanisms in the cell. The high immunological activity of the plant-derived nanocapsulated adjuvant Sapomax may be used to enhance the efficacy of vaccines.
Subject(s)
Adjuvants, Immunologic/administration & dosage , Immunity, Innate/drug effects , Saponaria/chemistry , Vaccines/immunology , Adjuvants, Immunologic/genetics , Animals , Cytokines/immunology , Drug Compounding , Female , Male , Mice , Mice, Inbred BALB C , Nanocapsules , Th1 Cells/drug effects , Th1 Cells/immunology , Th2 Cells/drug effects , Th2 Cells/immunologyABSTRACT
Avian pathogenic Escherichia coli (APEC) bacteria are one of the main problems of the poultry industry. An effective way to combat colibacillosis is to use a phage preparation that lyses the bacteria. Here, we report the isolation of an E. coli-infecting phage, CEC_KAZ_2018, isolated from soil.
ABSTRACT
Newcastle disease virus (NDV) infects domesticated and wild birds throughout the world and has the possibility to cause outbreaks in chicken flocks in future. To assess the evolutionary characteristics of 10 NDV strains isolated from chickens in Kazakhstan during 1998 we investigated the phylogenetic relationships among these viruses and viruses described previously. For genotyping, fusion (F) gene phylogenetic analysis (nucleotide number 47-421) was performed using sequences of Kazakhstanian isolates as compared to sequences of selected NDV strains from GenBank. Phylogenetic analysis showed that all newly characterized strains belonged to the genetic group designated as VIIb. All strains possessed a virulent fusion cleavage site (RRQRR/F) belonging to velogenic or mesogenic pathotypes with intracerebral pathogenicity indexes (ICPI) varying from 1.05 to 1.87.
