Antiviral activity of phosphorylated Radix Cyathulae officinalis polysaccharide against Canine Parvovirus in vitro

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Antiviral activity of phosphorylated Radix Cyathulae officinalis polysaccharide against Canine Parvovirus in vitro

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Antiviral activities of flavonoids isolated from the bark of Rhus verniciflua stokes against fish pathogenic viruses In Vitro
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An 80% methanolic extract of Rhus verniciflua Stokes bark showed significant anti-viral activity against fish pathogenic infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV) in a cell-based assay measuring virus-induced cytopathic effect (CPE). Activity-guided fractionation and isolation for the 80% methanolic extract of R. verniciflua yielded the most active ethyl acetate fraction, and methyl gallate (1) and four flavonoids: fustin (2), fisetin (3), butin (4) and sulfuretin (5). Among them, fisetin (3) exhibited high antiviral activities against both IHNV and VHSV showing EC(50) values of 27.1 and 33.3 μM with selective indices (SI = CC(50)/EC(50)) more than 15, respectively. Fustin (2) and sulfuretin (5) displayed significant antiviral activities showing EC50 values of 91.2-197.3 μM against IHNV and VHSV. In addition, the antiviral activity of fisetin against IHNV and VHSV occurred up to 5 hr post-infection and was not associated with direct virucidal effects in a timed addition study using a plaque reduction assay. These results suggested that the bark of R. verniciflua and isolated flavonoids have significant anti-viral activity against IHNV and VHSV, and also have potential to be used as anti-viral therapeutics against fish viral diseases.

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Molecular mechanisms behind the anti corona virus activity of small metal oxide nanoparticles.
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The recent COVID-19 pandemic has set a strong quest for advanced understanding of possible tracks in abating and eliminating viral infections. In the view that several families of "pristine" small oxide nanoparticles (NPs) have demonstrated viricidal activity against SARS-CoV-2, we studied the effect of two NPs, with presumably different reactivity, on two viruses aiming to evaluate two "primary suspect" routes of their antiviral activity, either specific blocking of surface proteins or causing membrane disruption. The chosen NPs were non-photoactive 3.5 nm triethanolamine terminated (surface capped) titania TiO2 NPs (TATT) and ultrasmall (1.1 nm) silicotungstate polyoxometalate (POM) NPs. The former were expected to both, interact with viral surface proteins as well as strongly complex with phosphate groups whereas the latter was not expected to form surface complexes. We demonstrated that expectedly, POM NPs up to 1.25 mM (4.5 mg l-1) had no significant antiviral activity towards neither of the used viruses, an enveloped transmissible gastroenteritis virus (TGEV) belonging to coronaviruses and non-enveloped encelomyocarditis virus (EMCV). At the same time, TATT NPs exhibited statistically significant (p < 0.05) antiviral activity against TGEV starting from 0.125 mM (12 μg ml-1). However, no antiviral activity of TATT against non-enveloped EMCV was detected. The observation that TATT NPs showed activity only against enveloped viruses and at relatively high concentrations suggests that the effect could be related with complexation with phospholipids. Possible chemical mechanism of viral membrane disruption was investigated by a variable temperature NMR study of NP complexation with model organic phosphate molecules, proving TATT to strongly interact with them and POM remain unreacted. Viral membrane disruption by TATT NPs was additionally confirmed by demonstraing RNA leackage from TGEV upon contact with those NPs. Therefore, our study proved a new mechanism of antiviral action of titania NPs in the dark which involved membrane disruption proceeding via direct surface complexation.

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Antiviral activity of water extracts of some medicinal and nutritive plants from the Apiaceae family
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During the past two decades, several human infections with avian influenza H5N1 virus have been reported. An increase in the recorded cases of human viral infections led to more public health concern, because of their potential pandemic proportions in the human's society. Moreover, an increase in the cases of drug-resistant influenza A virus has brought the urgent need for alternative anti-influenza drugs. In the present study, water extracts from eight commonly available medicinal and nutritive plants from the Apiaceae family including; Dill, Celery, Caraway, Coriander, Cumin, Fennel, Anise, and Parsley were prepared. The cytotoxicity of each of extract was individually determined in the Madin–Darby canine kidney (MDCK) cells. Thereafter, these extracts were investigated for their in vitro antiviral activities against the avian influenza H5N1 virus infection. Current results revealed that water extracts of the eight plants showed antiviral inhibitory activities with percentages ranging from 0- 71%. Among the tested plants, only anise plant (Pimpeniella anisum) had significant antiviral activity against the avian influenza H5N1 virus. Thus, the mode of action of this effective anise extract was investigated against the same virus. It was found that water extract of the anise plant induced virucidal effect, as well as direct effect on replication of the avian influenza H5N1 virus. The aim of the present study was to shed light on searching for alternative therapeutic sources for future treatment of the H5N1 influenza virus infection.

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In Vitro antiviral activity of red alga, Polysiphonia morrowii extract and its bromophenols against fish pathogenic infectious hematopoietic necrosis virus and infectious pancreatic necrosis virus
  • Feb 1, 2011
  • The Journal of Microbiology
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Our previous investigation revealed that 80% methanolic extract of the red alga Polysiphonia morrowii has significant antiviral activities against fish pathogenic viruses, infectious hematopoietic necrosis virus (IHNV) and infectious pancreatic necrosis virus (IPNV). The present study was conducted to identify compounds attributed for its antiviral activities and investigate their antiviral activities against IHNV and IPNV. Activity-guided fractionation for 80% methanolic extract of Polysiphonia morrowii using a cell-based assay measuring virus-induced cytopathic effect (CPE) on cells yielded a 90% methanolic fraction, which showed the highest antiviral activity against both viruses among fractions yielded from the extract. From the fraction, two bromophenols were isolated and identified as 3-bromo-4,5-dihydroxybenzyl methyl ether (1) and 3-bromo-4,5-dihydroxybenzaldehyde (2) based on spectroscopic analyses. For both compounds, the concentrations to inhibit 50% of flounder spleen cell (FSP cell) proliferation (CC(50)) and each viral replication (EC(50)) were measured. In the pretreatment test, 3-bromo-4,5-dihydroxybenzyl methyl ether (1) and 3-bromo-4,5-dihy-droxybenzaldehyde (2) exhibited significant antiviral activities showing selective index values (SI = CC(50)/EC(50)) of 20 to 42 against both IHNV and IPNV. In direct virucidal test, 3-bromo-4,5-dihydroxybenzyl methyl ether (1) showed significant antiviral activités against both viruses while 3-bromo-4,5-dihydroxybenzaldehyde (2) was significantly effective against only IHNV. Although antiviral efficacies of both compounds against IHNV and IPNV were lower than those of ribavirin used as a positive control, our findings suggested that the red alga Polysiphonia morrowii and isolated two bromophenols may have potential as a therapeutic agent against fish viral diseases.

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Double-Winged 3-Hydroxypyrimidine-2,4-diones: Potent and Selective Inhibition against HIV-1 RNase H with Significant Antiviral Activity.
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Human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated ribonuclease H (RNase H) remains the only virally encoded enzymatic function yet to be exploited as an antiviral target. One of the possible challenges may be that targeting HIV RNase H is confronted with a steep substrate barrier. We have previously reported a 3-hydroxypyrimidine-2,4-dione (HPD) subtype that potently and selectively inhibited RNase H without inhibiting HIV in cell culture. We report herein a critical redesign of the HPD chemotype featuring an additional wing at the C5 position that led to drastically improved RNase H inhibition and significant antiviral activity. Structure-activity relationship (SAR) concerning primarily the length and flexibility of the two wings revealed important structural features that dictate the potency and selectivity of RNase H inhibition as well as the observed antiviral activity. Our current medicinal chemistry data also revealed that the RNase H biochemical inhibition largely correlated the antiviral activity.

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Evaluation of Essential Oils and Extracts of Rose Geranium and Rose Petals as Natural Preservatives in Terms of Toxicity, Antimicrobial, and Antiviral Activity
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Essential oils (EOs) and extracts of rose geranium (Pelargonium graveolens) and petals of rose (Rosa damascena) have been fully characterized in terms of composition, safety, antimicrobial, and antiviral properties. They were analyzed against Escherichia coli, Salmonella enterica serovar Typhimurium, Staphylococcus aureus, Aspergillus niger, and Adenovirus 35. Their toxicity and life span were also determined. EO of P. graveolens (5%) did not retain any antibacterial activity (whereas at 100% it was greatly effective against E. coli), had antifungal activity against A. niger, and significant antiviral activity. Rose geranium extract (dilutions 25−90%) (v/v) had antifungal and antibacterial activity, especially against E. coli, and dose-dependent antiviral activity. Rose petals EO (5%) retains low inhibitory activity against S. aureus and S. Typhimurium growth (about 20−30%), antifungal activity, and antiviral activity for medium to low virus concentrations. Rose petals extract had significant antibacterial activity at dilutions of 25−90%, especially against E. coli and S. Typhimurium, antifungal, and the most potent antiviral activity. None of the EOs and extracts were toxic in dilutions of up to 5% and 90%, respectively. Finally, all materials had a life span of more than eight weeks. These results support the aspect that rose petals and rose geranium EOs, and extracts, have beneficial antimicrobial and antiviral properties and they can be used as natural preservatives.

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Antiviral activity of a hot water extract of black soybean against a human respiratory illness virus.
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Significant antiviral activity against respiratory illness viruses has been found in a hot-water extract of black soybean. This black soybean extract showed significant antiviral activity against human adenovirus type 1 and coxsackievirus B1 in a dose-dependent manner, while the hot-water extract from common yellowish soybean showed only weak activity. The antiviral activity could not be extracted from the black soybean by 70% aqueous ethanol, suggesting that saponin in the seed did not contribute to this activity. The antiviral activity was only recovered from cotyledons and not from seed coats with the hot water, showing that the activity was distributed in the cotyledons and that antocyanins in the black soybean seed coats did not contribute to the antiviral activity. The antiviral compound(s) in the black soybean was partially purified by up to 166 times by a combination of gel filtration, reversed phase HPLC, and ion-exchange HPLC. The partially purified antiviral compound showed hydrophilic and anionic properties, and a maximum absorption at 260 nm, suggesting that this antiviral fraction may contain a phenyl group(s). On the other hand, an amino acid analysis with the acid hydrolyzate and a neutral sugar analysis showed that the antiviral compound from black soybean might not be a polypeptide or glycoconjugate bearing neutral sugar(s).

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Hydrogen sulfide is an important endogenous mediator that has been the focus of intense investigation in the past few years, leading to the discovery of its role in vasoactive, cytoprotective and anti-inflammatory responses. Recently, we made a critical observation that H2S also has a protective role in paramyxovirus infection by modulating inflammatory responses and viral replication. In this study we tested the antiviral and anti-inflammatory activity of the H2S slow-releasing donor GYY4137 on enveloped RNA viruses from Ortho-, Filo-, Flavi- and Bunyavirus families, for which there is no FDA-approved vaccine or therapeutic available, with the exception of influenza. We found that GYY4137 significantly reduced replication of all tested viruses. In a model of influenza infection, GYY4137 treatment was associated with decreased expression of viral proteins and mRNA, suggesting inhibition of an early step of replication. The antiviral activity coincided with the decrease of viral-induced pro-inflammatory mediators and viral-induced nuclear translocation of transcription factors from Nuclear Factor (NF)-kB and Interferon Regulatory Factor families. In conclusion, increasing cellular H2S is associated with significant antiviral activity against a broad range of emerging enveloped RNA viruses, and should be further explored as potential therapeutic approach in relevant preclinical models of viral infections.

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SiRNA-mediated suppression of Japanese encephalitis virus replication in cultured cells and mice
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Japanese encephalitis virus (JEV) is a major cause of viral encephalitis in South-East Asia and there is a pressing need to develop novel therapeutic options against it. Gene silencing by RNA interference has therapeutic potential by way of degrading the RNA genome of JEV. Four small hairpin RNAs (shRNAs) targeting different locations in the JEV genome were evaluated for antiviral activity against JEV in different cell lines and the mouse model of disease. shN8010, an shRNA targeting the NS5-coding sequence of JEV, had significant antiviral activity in cultured cells. JEV titres were suppressed by 99% in human embryonic kidney cells at 24 h post-infection (p.i.) when shN8010 was delivered using a plasmid. Further, shN8010 delivered using recombinant adenovirus caused 99% and 95% suppression of JEV titres at 24 h p.i. in porcine stable kidney and Vero cells, respectively. In Neuro-2a cells, JEV titres at 24 h p.i. were suppressed by 90% when shN8010 was delivered using a recombinant adenovirus or retrovirus. Four-week-old FvB/J mice treated intracerebrally with recombinant adenovirus-delivered shN8010 1 week prior to lethal intraperitoneal JEV challenge showed no protection, although the mean survival time was prolonged. In a similar experiment, retrovirus-delivered shN8010 provided 100% protection to mice following the lethal JEV challenge. NS5-targeting shRNA (shN8010) had very significant antiviral activity in both cultured cells and the mouse model of JEV infection.

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