Anti-influenza A virus activity of flavonoids in vitro: a structure-activity relationship.

Secondary plant metabolites from food extracts, namely daidzein, quercetin, and luteolin, exhibit anti-influenza virus effects, with IC50 values of 143.6, 274.8, and 8.0 µM, respectively. The activities of these metabolites differ depending on the functional groups. Therefore, in this study, we focused on members of the flavonoid group, and investigated the anti-influenza viral effects of different flavonoid classes (flavone, isoflavone, flavonol, flavanone, and flavan-3-ol) in vitro. The IC50 values were 4.9-82.8 µM, 143.6 µM, 62.9-477.8 µM, 290.4-881.1 µM, and 22.9-6717.2 µM, respectively, confirming their activity. The modifying group factors (number, position, type) in the flavonoid skeleton may be significantly related to the anti-influenza virus activity. Moreover, time-of-addition assay revealed that the mechanism of inhibition varied for the different classes; for example, flavonoids that inhibit virus adsorption or the early stage of viral growth. Interestingly, all the examined flavonoids inhibited the late stages of viral growth, suggesting that flavonoids mainly inhibit the late events in viral growth before the release of viral particles. Additionally, apigenin might be effective against oseltamivir-resistant strains. Our results may be important in the development of anti-influenza virus therapeutic strategies in the future.

Inhibition of influenza virus replication by Apiaceae plants, with special reference to Peucedanum japonicum (Sacna) constituents.

ETHNOPHARMACOLOGICAL RELEVANCE: Apiaceae plants possess various pharmacological properties, such as antimicrobial, antioxidant, hypoglycemic, hypolipidemic, anxiolytic, analgesic, anti-inflammatory, anti-convulsant, and anti-cancer activities; however, data on their antiviral activity are limited. Peucedanum japonicum, also known as Sacna, is a plant used as food and as a traditional folk medicine for treating coughs. However, the active components in the leaves of this plant are yet unexplored. AIM OF THE STUDY: To assess Apiaceae plants, especially Peucedanum japonicum, with anti-viral activity, and the function and antiviral potential of Sacna constituents, considering the emergence of influenza virus strains resistant to the currently available drugs. MATERIALS AND METHODS: We prepared grinds of the freeze-dried leaves and roots of the Apiaceae family and the hot water extracts. The antiviral activities of the extracts were determined by focus formation reduction assay. In the time-of-addition assay, the test medium containing Sacna extract at 2 mg/mL was added at -1 to 0 h (adsorption) or from 0 to 4, 4 to 8, or 0 to 8 h (replication). The Sacna extract was separated by reversed-phase flash column chromatography using an Isolera Spektra system. The antiviral activity of each fraction was then determined using the focus formation reduction assay. The active fraction was analyzed using an LC20ADXR high performance liquid chromatography system equipped with a microTOF-QII quadrupole time-of-flight tandem mass spectrometer. RESULTS: All examined extracts of Apiaceae plants showed anti-influenza activity. Sacna extract most strongly inhibited the replication of influenza viruses. Individual components of Sacna possess antiviral activities against the influenza A/PR/8/34 virus. Sacna was found to inhibit the multiplication of A (H1N1 and H3N2) types and B types of influenza viruses, including amantadine-resistant and oseltamivir-resistant viruses. Sacna also inhibited influenza infection during viral replication. However, Sacna did not inhibit influenza infection during cell adsorption and did not suppress hemagglutination inhibition or cell fusion. Further, our findings suggest that the antiviral compounds in Sacna include flavonoids (quercetin and luteolin) and other polyphenols (caffeic acid, hymecromone, and umbelliferone). Although several effective compounds in Sacna inhibit multiple steps of viral replication, caffeic acid, which was increased by heat treatment at the time of extraction, significantly inhibited only the late period of viral growth, similar to the Sacna extract, indicating that it is the major component responsible for the antiviral activity of Sacna. CONCLUSIONS: Apiaceae plants possess antiviral activity. Caffeic acid is the major component responsible for the antiviral activity of Sacna. To our knowledge, this is the first report regarding the anti-influenza virus activity of Sacna. Overall, these results indicate that Sacna has potential as a novel treatment against influenza A and B viruses.

Antiviral Activity and Underlying Action Mechanism of Euglena Extract against Influenza Virus.

It is difficult to match annual vaccines against the exact influenza strain that is spreading in any given flu season. Owing to the emergence of drug-resistant viral strains, new approaches for treating influenza are needed. Euglena gracilis (hereinafter Euglena), microalga, used as functional foods and supplements, have been shown to alleviate symptoms of influenza virus infection in mice. However, the mechanism underlying the inhibitory action of microalgae against the influenza virus is unknown. Here, we aimed to study the antiviral activity of Euglena extract against the influenza virus and the underlying action mechanism using Madin-Darby canine kidney (MDCK) cells. Euglena extract strongly inhibited infection by all influenza virus strains examined, including those resistant to the anti-influenza drugs oseltamivir and amantadine. A time-of-addition assay revealed that Euglena extract did not affect the cycle of virus replication, and cell pretreatment or prolonged treatment of infected cells reduced the virus titer. Thus, Euglena extract may activate the host cell defense mechanisms, rather than directly acting on the influenza virus. Moreover, various minerals, mainly zinc, in Euglena extract were found to be involved in the antiviral activity of the extract. In conclusion, Euglena extract could be a potent agent for preventing and treating influenza.

Anti-Influenza Virus Activity of Adlay Tea Components.

Our previous study showed anti-influenza virus activity in adlay tea prepared from adlay seeds, naked barley seeds, soybean, and cassia seeds. In this study, we evaluated the anti-influenza virus activity of each component of this tea and analyzed their active ingredients. Each component was roasted and extracted in hot water; the extracts were tested for antiviral activity and their mechanisms of action were studied. All the tea components showed antiviral activity against the H1N1 and H3N2 influenza subtypes and against influenza B. The viral stages inhibited by the components were virus adsorption and replication in proliferative process, suggesting that the action mechanisms of the components might differ from those of oseltamivir acid. Of the tea components, soybean showed the strongest activity. Therefore, we analyzed its active ingredients by liquid chromatography quadruple time-of-flight mass spectrometry (LC/qTOF-MS) and daidzein and glycitein were detected as active ingredients. Here, anti-influenza virus action of glycitein was the first report.

Inhibition of influenza virus replication by adlay tea.

BACKGROUND: The present study was conducted aiming to examine the antiviral activity of adlay tea and its components against influenza viruses. We further aimed to clarify the mechanism by which these components regulate virus replication. RESULTS: Adlay tea at a concentration suitable for drinking inhibited the multiplication of influenza viruses. Moreover, our results suggest that individual components of the tea had antiviral activities against the influenza A/PR/8/34 virus. Adlay tea inhibited multiplication of the H1N1, H3N2 and B types of influenza virus, including oseltamivir-resistant viruses. In addition, adlay tea inhibited influenza infection during the periods of virus adsorption to the cell and virus replication. Adlay tea did not suppress hemagglutination inhibition or cell fusion, although it slightly inhibited virus binding to Malin Darby canine kidney cells. Furthermore, our findings suggest that the antiviral compounds included in adlay tea were ingredients other than polyphenols and that there were several types of effective compounds in adlay tea inhibiting several steps of viral replication. CONCLUSION: The results of the present study demonstrate that adlay tea had antiviral effects against influenza viruses. Our findings with respect to adlay tea suggest that the polyphenols might have a small influence on its antiviral activity and that other ingredients might have more influence. © 2017 Society of Chemical Industry.

Human herpesvirus 7 open reading frame U12 encodes a functional beta-chemokine receptor.

Human herpesvirus 7 (HHV-7), which belongs to the betaherpesvirus subfamily, infects mainly CD4+ T cells in vitro and infects children during infancy. After the primary infection, HHV-7 becomes latent. HHV-7 contains two genes (U12 and U51) that encode putative homologs of cellular G-protein-coupled receptors. To analyze the biological function of the U12 gene, we cloned the gene and expressed the U12 protein in cells. The U12 gene encoded a calcium-mobilizing receptor for the EBI1 ligand chemokine-macrophage inflammatory protein 3beta (ELC/MIP-3beta) but not for other chemokines, suggesting that the chemokine selectivity of the U12 gene product is distinct from that of the known mammalian chemokine receptors. These studies revealed that U12 activates distinct transmembrane signaling pathways that may mediate biological functions by binding with a beta-chemokine, ELC/MIP-3beta.