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Novel antiviral activity of mung bean sprouts against respiratory syncytial virus and herpes simplex virus −1: an in vitro study on virally infected Vero and MRC-5 cell lines

https://pubmed.ncbi.nlm.nih.gov/26062546/

Results: MBS extract showed reduction factors (RF) 2.2 × 10 and 0.5 × 10(2) for RSV and HSV-1, respectively. The 2 h incubation virucidal and prophylactic selectivity indices (SI) of MBS on RSV were 14.18 and 12.82 versus Ribavarin SI of 23.39 and 21.95, respectively, and on HSV-1, SI were 18.23 and 10.9 versus Acyclovir, 22.56 and 15.04, respectively. All SI values were >10 indicating that MBS has a good direct antiviral and prophylactic activities on both RSV and HSV-1. Moreover, interestingly, MBS extract induced vigorously IFNβ, TNFα, IL-1, and IL-6 cytokines in MRC-5 infected-treated group far more than other groups (P < 0.05) and induced TNFα and IL-6 in treated group more than infected group (P < 0.05).

Conclusions: MBS extract has potent antiviral and to a lesser extent, prophylactic activities against both RSV and HSV-1, and in case of HSV-1, these activities were comparable to Acyclovir. Part of the underlying mechanism(s) of these activities is attributed to MBS potential to remarkably induce antiviral cytokines in human cells. Hence, we infer that MBS methanol extract could be used as such or as purified active component in protecting and treating RSV and HSV-1 infections. More studies are needed to pinpoint the exact active components responsible for the MBS antiviral activities.

Tangeretin from Citrus reticulate Inhibits Respiratory Syncytial Virus Replication and Associated Inflammation in Vivo.

https://pubmed.ncbi.nlm.nih.gov/26468759/

Human respiratory syncytial virus (RSV) is a common pathogen that causes pneumonia and bronchiolitis in infants and young children. Our previous study showed that tangeretin from Citrus reticulate possessed potent in vitro anti-RSV effects comparable to that of ribavirin. Therefore, in this study, we investigated the in vivo anti-RSV activity of tangeretin in 3-week-old male BALB/c mice. A plaque reduction assay and fluorescence quantitative polymerase chain reaction (FQ-PCR) showed that tangeretin inhibited RSV replication in the lung of mice. Moreover, a luminex assay indicated tangeretin relieved RSV-induced lung inflammation by attenuating interleukin (IL)-1β secretion. Possible anti-inflammatory mechanisms of tangeretin were preliminarily explored using a RSV-infected macrophage model. A FQ-PCR, enzyme-linked immunosorbent assay (ELISA), and luciferase assay revealed that tangeretin inhibited RSV-induced inflammation by suppressing nuclear factor-κB (NF-κB) activation. This study demonstrates that tangeretin inhibited RSV replication and RSV-induced lung inflammation in vivo and may be useful in preventing and treating RSV infections and inflammation.

https://pubmed.ncbi.nlm.nih.gov/23123794/

Results: Fresh ginger dose-dependently inhibited HRSV-induced plaque formation in both HEp-2 and A549 cell lines (p<0.0001). In contrast, dried ginger didn't show any dose-dependent inhibition. 300 μg/ml fresh ginger could decrease the plaque counts to 19.7% (A549) and 27.0% (HEp-2) of that of the control group. Fresh ginger was more effective when given before viral inoculation (p<0.0001), particularly on A549 cells. 300 μg/ml fresh ginger could decrease the plaque formation to 12.9% when given before viral inoculation. Fresh ginger dose-dependently inhibited viral attachment (p<0.0001) and internalization (p<0.0001). Fresh ginger of high concentration could stimulate mucosal cells to secrete IFN-β that possibly contributed to counteracting viral infection.

Conclusions: Fresh, but not dried, ginger is effective against HRSV-induced plaque formation on airway epithelium by blocking viral attachment and internalization.

The objective of this study is to investigate the antiviral, anti-inflammatory, and antioxidant effects of the ethanol extract of Mentha piperita L. leaves (MPE). M. piperita L. leaves were extracted by reflux with ethanol. Total phenolic acid and total flavonoid content were determined. The antiviral activity of MPE against the respiratory syncytial virus (RSV) and the anti-inflammatory activity were evaluated in vitro. The levels of key pre-inflammatory mediators and cytokines including nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and prostaglandin E2 (PGE2) were determined. The antioxidant activities were also evaluated using a colorimetry method. MPE contained high levels of phenolic acid and flavonoid, showed antiviral activity against RSV with a high selectivity index, and significantly decreased the production of NO, TNF-α, IL-6, and PGE2 in lipopolysaccharide-stimulated RAW 264.7 cells. Meanwhile, MPE showed potential free-radical scavenging activities. These results indicate that Mentha piperita L. might be a good source of medicinal plants.

Anti-inflammatory effects of curcumin-loaded niosomes on respiratory syncytial virus infection in a mice model.

https://pubmed.ncbi.nlm.nih.gov/35417322/

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in paediatrics. While antivirals are apparent candidates to treat RSV-induced diseases, they have not yet met expectations and have remained in infancy. There is growing evidence to suggest that modulating the exacerbated inflammation during RSV infection can improve disease outcome. Curcumin-loaded niosomes have anti-inflammatory effects against RSV-induced respiratory disease by reducing immune cells' infiltration and inflammatory cytokines' production. This study evaluated the effects of curcumin-loaded niosomes on RSV-induced immunopathology in a mice model. Curcumin-loaded niosomes were prepared using the thin-film hydration method and characterized in vitro. Female Balb/c mice were infected by RSV-A2 and treated daily with curcumin-loaded niosomes. The potential anti-inflammatory effects of curcumin-loaded niosomes were evaluated on day 5 after infection. Using curcumin-loaded niosomes decreased immune cell influx and the inflammatory mediators (MIP-1α, TNF-α and IFN-γ) production in the lung, resulting in alleviated lung pathology following RSV infection. These findings indicate that curcumin-loaded niosomes have anti-inflammatory potential and could be a promising candidate to alleviate RSV-associated immunopathology.

Supplements

https://pubmed.ncbi.nlm.nih.gov/9863072/

An intervention study was conducted in 75 young children under one year hospitalized with pneumonia or bronchiolitis caused by respiratory syncytial virus (RSV) to evaluate therapeutic effectiveness of selenium (Se) supplement on acute respiratory lower tract infection caused by RSV with randomly controlled and double-masked method. Trial subjects were divided into two groups, one with 37 children in routine treatment and the other with 38 children in routine treatment plus Se supplement. The control group derived from 35 normal children during their physical check-up in the out-patient department. Sodium selenite was supplemented orally with 1 mg on the second day of hospitalization. Results showed that days needed for their relief of symptoms and signs were fewer in Se supplement group than that in controls and recovery in indicators of cell immune was better in the former than that in the latter. Levels of Se and glutathione peroxidase in plasma and white cells could be increased by Se supplement. It suggests that Se supplement can promote recovery from RSV infection.

Effect of zinc salts on respiratory syncytial virus replication.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC353050/

Zinc supplementation decreases the morbidity of lower respiratory tract infection in pediatric patients in the developing world. We sought to determine if zinc mediates a specific inhibitory effect against the major cause of pediatric lower respiratory tract disease, respiratory syncytial virus (RSV). We determined the in vitro inhibitory effect of three zinc salts (zinc acetate, lactate, and sulfate) on the replication of RSV at various concentrations of 10 and 1 mM and 100 and 10 μM. The degree of inhibition of RSV replication was examined in the presence of zinc during preincubation, adsorption, or penetration and was compared with that caused by salts of other divalent cations. Complete inhibition of RSV plaque formation was observed at 1 and 10 mM, representing reductions that were ≥10⁶-fold. At the lowest concentration tested, 10 μM, we observed ≥1,000-fold reductions in RSV yield when zinc was present during preincubation, adsorption, penetration, or egress of virus. The therapeutic indices, determined as ratios of 50% toxicity concentration to 50% inhibitory concentration, were 100, 150, and 120 for zinc acetate, zinc lactate, and zinc sulfate, respectively. The inhibitory effect of zinc salts on RSV was concentration dependent and was not observed with other salts containing divalent cations such as calcium, magnesium, and manganese. RSV plaque formation was prevented by pretreatment of HEp-2 cell monolayer cultures with zinc or by addition of zinc to methylcellulose overlay media after infection. The results of this study suggest that zinc mediates antiviral activity on RSV by altering the ability of the cell to support RSV replication.

Herbal supplements

https://www.spandidos-publications.com/10.3892/ijmm.2014.1750

Panax ginseng has been known to have a number of immuno-modulatory effects. In this study, we investigated whether Panax Korean red ginseng extract (KRGE) has in vitro and in vivo antiviral effects on respiratory syncytial virus (RSV) infection. KRGE improved the survival of human lung epithelial cells against RSV infection and inhibited RSV replication. In addition, KRGE treatment suppressed the expression of RSV-induced inflammatory cytokine genes (IL-6 and IL-8) and the formation of reactive oxygen species in epithelial cell cultures. Oral administration of mice with KRGE resulted in lowering lung viral loads after RSV infection. Additionally, the in vivo effects of KRGE showed an enhanced level of interferon-γ (IFN-γ) producing dendritic cells subsequent to RSV infection. Taken together, these results suggested that KRGE has antiviral activity against RSV infection.

https://pubmed.ncbi.nlm.nih.gov/11397509/

A liquid extract from Eleutherococcus senticosus roots (iSiberian Ginseng) inhibited the productive replication of human rhinovirus (HRV), respiratory syncytial virus (RSV) and influenza A virus in cell cultures ……...

https://pubmed.ncbi.nlm.nih.gov/25939536/

Respiratory syncytial virus (RSV) causes severe lower respiratory tract infection and poses a major public health threat worldwide. No effective vaccines or therapeutics are currently available; berberine, an isoquinoline alkaloid from various medicinal plants, has been shown to exert antiviral and several other biological effects. Recent studies have shown that p38 mitogen-activated protein kinase (MAPK) activity is implicated in infection by and replication of viruses such as RSV and the influenza virus. Because berberine has previously been implicated in modulating the activity of p38 MAPK, its effects on RSV infection and RSV-mediated p38 MAPK activation were examined. Replication of RSV in epithelial cells was significantly reduced by treatment with berberine. Berberine treatment caused decrease in viral protein and mRNA syntheses. Similar to previously reported findings, RSV infection caused phosphorylation of p38 MAPK at a very early time point of infection, and phosphorylation was dramatically reduced by berberine treatment. In addition, production of interleukin-6 mRNA upon RSV infection was significantly suppressed by treatment with berberine, suggesting the anti-inflammatory role of berberine during RSV infection. Taken together, we showed that berberine, a natural compound already proven to be safe for human consumption, suppresses the replication of RSV. In addition, the current study suggests that inhibition of RSV-mediated early p38 MAPK activation, which has been implicated as an early step in viral infection, as a potential molecular mechanism.

Aesculus hippocastanum L. seed extract shows virucidal and antiviral activities against respiratory syncytial virus (RSV) and reduces lung inflammation in vivo.

https://pubmed.ncbi.nlm.nih.gov/30711418/

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease and bronchiolitis in children worldwide. No vaccine or specific, effective treatment is currently available. β-escin is one of the main bioactive constituents of Aesculus hippocastanum L. (Hippocastanaceae) seed extract (AH), and both β-escin and AH have demonstrated a beneficial role in clinical therapy because of their anti-edematous, anti-inflammatory and antioxidative effects. Besides, we have reported that β-escin and AH show virucidal, antiviral and immunomodulatory activities against the enveloped viruses HSV-1, VSV and Dengue virus in vitro. In this study, we demonstrate that β-escin and AH have virucidal and antiviral activities against RSV, as well as NF-κB, AP-1 and cytokine modulating activities in RSV infected epithelial and macrophage cell lines in vitro. Besides, in a murine model of pulmonary RSV infection, AH treatment improves the course of acute disease, evidenced by decreased weight loss, reduced RSV lung titers, and attenuated airway inflammation. In contrast, even though β-escin showed, similarly to AH, antiviral and immunomodulatory properties in vitro, it neither reduces viral titers nor attenuates lung injury in vivo. Thus, our data demonstrate that AH restrains RSV disease through antiviral and immunomodulatory effect.

Esoteric

Antiviral and Immunomodulatory Activity of Silver Nanoparticles in Experimental RSV Infection.

https://pubmed.ncbi.nlm.nih.gov/31398832/

Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infection in children for which no specific treatment option is available. The RSV virion contains two surface glycoproteins (F and G) that are vital for the initial phases of infection, making them critical targets for RSV therapeutics. Recent studies have identified the broad-spectrum antiviral properties of silver nanoparticles (AgNPs) against respiratory pathogens, such as adenovirus, parainfluenza, and influenza. AgNPs achieve this by attaching to viral glycoproteins, blocking entry into the host cell. The objective of this study was to evaluate the antiviral and immunomodulatory effects of AgNPs in RSV infection. Herein we demonstrate AgNP-mediated reduction in RSV replication, both in epithelial cell lines and in experimentally infected BALB/c mice. Marked reduction in pro-inflammatory cytokines (i.e., IL-1α, IL-6, TNF-α) and pro-inflammatory chemokines (i.e., CCL2, CCL3, CCL5) was also observed. Conversely, CXCL1, G-CSF, and GM-CSF were increased in RSV-infected mice treated with AgNPs, consistent with an increase of neutrophil recruitment and activation in the lung tissue. Following experimental antibody-dependent depletion of neutrophils, the antiviral effect of AgNPs in mice treated was ablated. To our knowledge, this is the first in vivo report demonstrating antiviral activity of AgNPs during RSV infection.

Three novel bisflavonol derivatives, Hovenianins A-C, along with 12 known flavonoids were isolated and identified from the seeds of Hovenia dulcis Thunb. Their structures were established on the basis of spectroscopic methods (MS, UV, IR, 1D and 2D NMR) and electronic circular dichroism experiments. Hovenianin A (1) was the first dimer of flavonol linked dihydroflavonol via the B rings at C-2' and C-2″'positions to be found in nature. While Hovenianins BC (2-3) were a pair of diastereoisomeric bis-dihydroflavonols firstly reported in the Hovenia genus. The in vitro antiviral activity against respiratory syncytium virus (RSV) were evaluated by cytopathic effect (CPE) reduction assay. As a result, compounds 4, 5, and 10 displayed better antiviral effect against RSV A2 strains.

The herbs Plantago asiatica and Clerodendrum trichotomum have been commonly used for centuries in indigenous and folk medicine in tropical and subtropical regions of the world. In this study, we show that extracts from these herbs have antiviral effects against the respiratory syncytial virus (RSV) in vitro cell cultures and an in vivo mouse model. Treatment of HEp2 cells and A549 cells with a non-cytotoxic concentration of Plantago asiatica or Clerodendrum trichotomum extract significantly reduced RSV replication, RSV-induced cell death, RSV gene transcription, RSV protein synthesis, and also blocked syncytia formation. Interestingly, oral inoculation with each herb extract significantly improved viral clearance in the lungs of BALB/c mice. Based on reported information and a high-performance liquid chromatography (HPLC) analysis, the phenolic glycoside acteoside was identified as an active chemical component of both herb extracts. An effective dose of acteoside exhibited similar antiviral effects as each herb extract against RSV in vitro and in vivo. Collectively, these results suggest that extracts of Plantago asiatica and Clerodendrum trichotomum could provide a potent natural source of an antiviral drug candidate against RSV infection.

Myrtucomvalones A–C, three unusual triketone–
sesquiterpene adducts from the leaves of Myrtus
communis ‘Variegata’

https://pubs.rsc.org/en/content/articlepdf/2017/ra/c7ra02260c

Three new triketone–sesquiterpene adducts, myrtucomvalones A–C (1–3), along with four known compounds (4–7) were isolated from the leaves of Myrtus communis ‘Variegata’. Compounds 1 and 2 are the first examples of triketone–cubebane hybrids with an unusual carbon skeleton. Their structures with absolute configurations were determined by spectroscopic data, single crystal X-ray diffraction and electronic circular dichroism (ECD) analyses. Compounds 1–7 displayed inhibitory activities against respiratory syncytial virus (RSV).