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1.
Nat Prod Commun ; 12(4): 599-602, 2017 Apr.
Article in English | MEDLINE | ID: mdl-30520604

ABSTRACT

Influenza A viruses are responsible for annual epidemics and occasional pandemics, which cause significant morbidity and mortality. The limited protection offered by influenza vaccination, and the emergence of drug-resistant influenza strains, highlight the urgent need for the development of novel anti-influenza drugs. However, the search for antiviral substances from the library of low molecular weight chemical compounds is limited. Thus, because of their natural diversity and accessibility, plants or plant-derived materials are rapidly becoming valuable sources for the discovery and development of new antiviral drugs. In this study, crude extracts of Aspalathus linearis, a plant reported to have anti-HIV activity, were evaluated in vitro for their activity against the influenza A virus Of the extracts tested, an alkaline extract of Aspalathus linearis demonstrated the strongest inhibition against influenza A virus and could also inhibit different.types of influenza viruses, including Oseltamivir-resistant influenza viruses A and B. Our time course of addition studies indicated that the alkaline extract of Aspalathus linearis exerts its antiviral effect predominantly during the late stages of the influenza virus replication process.


Subject(s)
Antiviral Agents/pharmacology , Aspalathus/chemistry , Orthomyxoviridae/drug effects , Plant Extracts/pharmacology , Humans , Influenza, Human/virology , Orthomyxoviridae/physiology , Virus Replication/drug effects
2.
Drug Discov Ther ; 10(4): 201-10, 2016.
Article in English | MEDLINE | ID: mdl-27558282

ABSTRACT

Influenza A and B virus infections are serious public health concerns globally. However, the concerns regarding influenza B infection have been underestimated. The currently used anti-influenza drugs have not provided equal efficacy for both influenza A and B viruses. Susceptibility to neuraminidase (NA) inhibitors has been observed to be lower for influenza B viruses than for influenza A viruses. Moreover, the emergence of resistance to anti-influenza drugs underscores the need to develop new drugs. Recently, we reported that methylglyoxal (MGO) suppressed influenza A virus replication in a strain-independent manner. Therefore, we hypothesize that MGO exhibits anti-influenza activity against B strains. This study aimed to evaluate the anti-influenza viral activity of MGO against influenza B strains by using Madin-Darby canine kidney (MDCK) cells. Several types of influenza B viruses were used to determine the activity of MGO. The susceptibilities of influenza A and B viruses to NA inhibitors were compared. MGO inhibited influenza B virus replication, with 50% inhibitory concentrations ranging from 23-140 µM, which indicated greater sensitivity of influenza B viruses than influenza A viruses. Our results show that MGO has potent inhibitory activity against influenza B viruses, including NA inhibitor-resistant strains.


Subject(s)
Antiviral Agents/pharmacology , Influenza B virus/drug effects , Pyruvaldehyde/pharmacology , Virus Replication/drug effects , Acids, Carbocyclic , Animals , Cyclopentanes/pharmacology , Dogs , Enzyme Inhibitors/pharmacology , Guanidines/pharmacology , In Vitro Techniques , Inhibitory Concentration 50 , Madin Darby Canine Kidney Cells , Neuraminidase/antagonists & inhibitors , Oseltamivir/pharmacology , Pyrans , Sialic Acids , Zanamivir/analogs & derivatives , Zanamivir/pharmacology
3.
Arch Med Res ; 46(1): 8-16, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25523147

ABSTRACT

BACKGROUND AND AIMS: Influenza virus infections are serious public health concerns worldwide that cause considerable mortality and morbidity. Moreover, the emergence of resistance to anti-influenza viral agents underscores the need to develop new anti-influenza viral agents and novel treatment strategies. Recently, we identified anti-influenza viral activity of manuka honey. Therefore, we hypothesized that methylglyoxal (MGO), a key component of manuka honey, may impart anti-influenza viral activity. The aim of this study was to evaluate the anti-influenza viral activity of MGO and its potential in combination treatments with neuraminidase (NA) inhibitors. METHODS: MDCK cells were used to evaluate anti-influenza viral activity. To evaluate the mechanism of MGO, plaque inhibition assays were performed. The synergistic effects of MGO and viral NA inhibitors were tested. RESULTS: MGO inhibited influenza virus A/WSN/33 replication 50% inhibitory concentration = 240 ± 190 µM; 50% cytotoxic concentration = 1.4 ± 0.4 mM; selective index (SI) = 5.8, which is related to its virucidal effects. Moreover, we found that MGO showed promising activity against various influenza strains. A synergistic effect was observed by a marked increase in SI of NA inhibitors at ∼1/100(th) of their single usage. A synergistic effect of MGO and oseltamivir was also observed against oseltamivir-resistant virus. CONCLUSIONS: Our results showed that MGO has potent inhibitory activity against influenza viruses and also enhanced the effect of NA inhibitors. Thus, the co-administration of MGO and NA inhibitors should be considered for treatment of influenza virus infections.


Subject(s)
Antiviral Agents/pharmacology , Influenza A virus/drug effects , Neuraminidase/antagonists & inhibitors , Oseltamivir/pharmacology , Pyruvaldehyde/pharmacology , Animals , Dogs , Drug Synergism , Drug Therapy, Combination , Enzyme Inhibitors/pharmacology , Influenza A Virus, H1N1 Subtype/drug effects , Influenza A Virus, H3N2 Subtype/drug effects , Influenza A Virus, H5N2 Subtype/drug effects , Inhibitory Concentration 50 , Madin Darby Canine Kidney Cells , Orthomyxoviridae Infections/drug therapy , Orthomyxoviridae Infections/virology , Virus Replication/drug effects
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