Hwa-Jung Choi

Antiviral activity of quercetin 7-rhamnoside against porcine epidemic diarrhea virus.

Abstract Porcine epidemic diarrhea virus (PEDV) is the predominant cause of severe entero-pathogenic diarrhea in swine. The lack of effective therapeutical treatment underlines the importance of research for new antivirals. In this study, we identified Q7R, which actively inhibited PEDV replication with a 50% inhibitory concentration (IC50) of 0.014μg/mL. The 50% cytotoxicity concentration (CC50) of Q7R was over 100μg/mL and the derived therapeutic index was 7142. Several structural analogues of Q7R, quercetin, apigenin, luteolin and catechin, also showed moderate anti-PEDV activity. Antiviral drugs and natural compounds revealed ribavirin, interferon-α, coumarin and tannic acid have relative weaker efficacy compared to Q7R. Q7R did not directly interact with or inactivate PEDV particles and affect the initial stage of PEDV infection by interfering of PEDV replication. Also, the effectiveness of Q7R against the other two viruses (TGEV, PRCV) was lower compared to PEDV. Q7R could be considered as a lead compound for development of anti-PEDV drugs to may be used to during the early stage of PEDV replication and the structure-activity data of Q7R may usefully guideline to design other related antiviral agents.

Inhibitory effects of quercetin 3-rhamnoside on influenza A virus replication

Influenza viruses cause significant morbidity and mortality in humans through epidemics or pandemics. The lack of effective therapeutical treatment underlines the importance of research for new antiviral compounds. Flavonoids widely exist in the plant kingdom, and their antiviral activities against various viruses have been recently reported. In this study, the anti-influenza A/WS/33 virus of quercetin 3-rhamnoside (Q3R) from Houttuynia cordata was evaluated using a cytopathic effect (CPE) reduction method, the assay results demonstrated that Q3R possessed strong anti-influenza A/WS/33 virus reducing the formation of a visible CPE. Q3R also did inhibit virus replication in the initial stage of virus infection by indirect interaction with virus particles. However, oseltamivir has relative weaker efficacy compared to Q3R. Therefore, these findings provide important information for the utilization of Q3R for influenza treatment.

Antiviral activity of raoulic acid from Raoulia australis against Picornaviruses.

RNA viruses are a major source of respiratory diseases worldwide. The lack of effective therapeutical treatment underlines the importance of research for new antiviral compounds. Raoulic acid is a principal ingredient of the plant Raoulia australis Hook. F. Antiviral assay using cytopathic effect (CPE) reduction method showed that raoulic acid possessed strong antiviral activity against human rhinovirus 2 (HRV2) with a 50% inhibition concentration (IC(50)) value of less than 0.1mug/ml, human rhinovirus 3 (HRV3) with a IC(50) value of 0.19 microg/ml, coxsackie B3 (CB3) virus with IC(50) values of 0.33 microg/ml, coxsackie B4 (CB4) virus with IC(50) values of 0.40 microg/ml, and enterovirus 71 (EV71) virus with IC(50) values of less than 0.1 microg/ml. However, the compound did not possess antiviral activity against influenza A (Flu A/PR, Flu A/WS, H1N1) and B viruses at four concentrations ranging from 0.1 to 100 microg/ml.

Anti-human rhinovirus activity of gallic acid possessing antioxidant capacity

Human rhinoviruses (HRVs) are a major cause of the common cold and until now there is no registered clinically effective antiviral chemotherapeutic agent for treatment of diseases caused by HRVs. Our previous report showed that gallic acid from Woodfordia fruticosa flowers possessed antioxidant activity. Many studies reported that antioxidants possess antiviral activities against various viruses. Therefore, we examined antiviral activity of gallic acid against HRVs and mode of its actions by observing the effect of gallic acid on HRV‐induced cytopathic effect (CPE) and the infectivity of HRV particles, and then carried out a time‐addition study. As a result, gallic acid actively inhibited HRV2 and ‐3 replications with antiviral activity more than 55% without cytotoxicity in human epitheloid carcinoma cervix (HeLa) cells at a concentration of 100 μg/mL. Also, ribavirin showed lower anti‐HRV3 activity than gallic acid and similar anti‐HRV3 activity to it. The addition of gallic acid to HRV‐infected HeLa cells directly reduced the formation of a visible CPE. Furthermore, gallic acid did directly interact or activate with HRV particles. Collectively, we concluded that the inhibition of HRV production by gallic acid is mainly due to a general action as an antioxidant and the mode of action derived from the inhibition of virus absorption. Copyright

Antiviral activity of ginsenosides against coxsackievirus B3, enterovirus 71, and human rhinovirus 3

Background Ginsenosides are the major components responsible for the biochemical and pharmacological actions of ginseng, and have been shown to have various biological activities. In this study, we investigated the antiviral activities of seven ginsenosides [protopanaxatriol (PT) type: Re, Rf, and Rg2; protopanaxadiol (PD) type: Rb1, Rb2, Rc, and Rd)] against coxsackievirus B3 (CVB3), enterovirus 71 (EV71), and human rhinovirus 3 (HRV3). Methods Assays of antiviral activity and cytotoxicity were evaluated by the sulforhodamine B method using the cytopathic effect (CPE) reduction assay. Results The antiviral assays demonstrated that, of the seven ginsenosides, the PT-type ginsenosides (Re, Rf, and Rg2) possess significant antiviral activities against CVB3 and HRV3 at a concentration of 100 μg/mL. Among the PT-type ginsenosides, only ginsenoside Rg2 showed significant anti-EV71 activity with no cytotoxicity to cells at 100 μg/mL. The PD-type ginsenosides (Rb1, Rb2, Rc, and Rd), by contrast, did not show any significant antiviral activity against CVB3, EV71, and HRV3, and exhibited cytotoxic effects to virus-infected cells. Notably, the antiviral efficacies of PT-type ginsenosides were comparable to those of ribavirin, a commonly used antiviral drug. Conclusion Collectively, our findings suggest that the ginsenosides Re, Rf, and Rg2 have the potential to be effective in the treatment of CVB3, EV71, and HRV3 infection.

Anti-Human Rhinoviral Activity of Polybromocatechol Compounds Isolated from the Rhodophyta, Neorhodomela aculeata

An extract of the red alga, Neorhodomela aculeata, exhibited antiviral activity against human rhinoviruses. Bioassay-guided purification was performed to yield six compounds, which were subsequently identified as lanosol (1) and five polybromocatechols (2–6) by spectroscopic methods, including 1D and 2D NMR and mass spectrometric analyses. Structurally, all of these compounds, except compound 5, contain one or two 2,3-dibromo-4,5-dihydroxyphenyl moieties. In a biological activity assay, compound 1 was found to possess antiviral activity with a 50% inhibitory concentration (IC50) of 2.50 μg/mL against HRV2. Compound 3 showed anti-HRV2 activity, with an IC50 of 7.11 μg/mL, and anti-HRV3 activity, with an IC50 of 4.69 μg/mL, without demonstrable cytotoxicity at a concentration of 20 μg/mL. Collectively, the results suggest that compounds 1 and 3 are candidates for novel therapeutics against two different groups of human rhinovirus.

Anti-Human Rhinovirus Activity of Raoulic Acid from Raoulia australis

Human rhinoviruses (HRVs), members of the Picornaviridae family, are composed of over 100 different virus serotypes. Until now there is no recorded clinically effective antiviral chemotherapeutic agent for treatment of diseases caused by HRVs. Our previous study of raoulic acid tested against serotype human rhinoviruses showed anti-HRV2 (species A) and -3 (species B) activities. In this study, raoulic acid was found to possess broad-spectrum antiviral activity against six HRVs with a 50% inhibition concentration of less than 9.5 microg/mL through inhibition of the cellular absorption of the HRV particles. Furthermore, the effect of raoulic acid on resistance of HRV5 exhibited to pleconaril was more pronounced than the effect on HRV1b, -6, -14, -15, and -40. However, ribavirin did possess weak antiviral activity against HRVs. Collectively, the results demonstrate that raoulic acid is a novel therapeutic candidate for two different groups of human rhinovirus.

Anti-human rhinovirus 2 activity and mode of action of quercetin-7-glucoside from Lagerstroemia speciosa.

Human rhinoviruses (HRVs) are a major cause of the common cold, but there is currently, no registered clinically effective antiviral chemotherapeutic agent for treatment of diseases caused by HRVs. In this study, we examined the antiviral activity of quercetin 7-glucoside (Q7G) from Lagerstroemia speciosa against human rhinovirus 2 (HRV2) using a cytopathic effect (CPE) reduction method. Furthermore, to elucidate the action of Q7G on HRV2 multiplication in more detail, we investigated the effect of Q7G on the infection cycle of HRV2 through time-of-addition study, reverse transcription-polymerase chain reaction analysis, and effects of Q7G on the infectivity of HRV2 particles. Q7G potently showed anti-HRV2 activity by reducing the formation of a visible CPE. Q7G also inhibited virus replication in the initial stage of virus infection by indirect interaction with virus particles, and ribavirin had a relative weaker efficacy compared to Q7G. Therefore, these data suggest that Q7G exerted its anti-HRV2 effect via the inhibition of virus replication in the early stage and these findings provide important information for the utilization of Q7G for HRV2 treatment.

Inhibitory Effects of Norwogonin, Oroxylin A, and Mosloflavone on Enterovirus 71

Severe complications associated with EV71 infections are a common cause of neonatal death. Lack of effective therapeutic agents for these infections underlines the importance of research for the development of new antiviral compounds. In the present study, the anti-EV71 activity of norwogonin, oroxylin A, and mosloflavone from Scutellaria baicalensis Georgi was evaluated using a cytopathic effect (CPE) reduction method, which demonstrated that all three compounds possessed strong anti-EV71 activity and decreased the formation of visible CPEs. Norwogonin, oroxylin A, and mosloflavone also inhibited virus replication during the initial stage of virus infection, and they inhibited viral VP2 protein expression, thereby inhibiting viral capsid protein synthesis. However, ribavirin has a relatively weaker efficacy compared to the other drugs. Therefore, these findings provide important information that will aid in the utilization of norwogonin, oroxylin A, and mosloflavone for EV71 treatment.

Antifungal Effect of Brachyglottis repanda Ethanol Extract.

The crude ethanol extract of B. repanda showed the cytotoxic activity against Polio virus (25% activity at 150 μg/disk) and the minor cytotoxic activity against BSC cells (African green monkey kidney) . However, the crude ethanol extract of B. repanda was non-toxic to murine leukaemia cells CCL 46 P388D1 (IC50, > 62,500 ng/ml) . Cytotoxic and antifungal activities were strongly shown by Fr. 64-3 which was eluted with 90% CH3CN/H2O, 100% CH3CN, and 50% CH3CN/H2O (SM 2 at 150 μg/disk) . The fraction 64-3 also showed the most cytotoxic activity against murine leukaemia cells (128 mg, IC50 10,051 ng/ml at 75 μg/disk) . These results suggest that this fraction has a potent antifungal activity against the dermatophytic fungus Trichophyton mentagrophytes ATCC 28185.