PMID: 

Viruses. 2020 Feb 4 ;12(2). Epub 2020 Feb 4. PMID: 32033244

Abstract Title: 

Antiviral Effect of Epigallocatechin Gallate via Impairing Porcine Circovirus Type 2 Attachment to Host Cell Receptor.

Abstract: 

The green tea catechin epigallocatechin gallate (EGCG) exhibits antiviral activity against various viruses. Whether EGCG also inhibits the infectivity of circovirus remains unclear. In this study, we demonstrated the antiviral effect of EGCG on porcine circovirus type 2 (PCV2). EGCG targets PCV2 virions directly and blocks the attachment of virions to host cells. The microscale thermophoresis assay showed EGCG could interact with PCV2 capsid protein in vitro with considerable affinity (Kd = 98.03± 4.76 μM), thereby interfering with the binding of the capsid to the cell surface receptor heparan sulfate. The molecular docking analysis of capsid-EGCG interaction identified the key amino acids which formed the binding pocket accommodating EGCG. Amino acids ARG51, ASP70, ARG73 and ASP78 of capsid were found to be critical for maintaining the binding, and the arginine residues were also essential for the electrostatic interaction with heparan sulfate. The rescued mutant viruses also confirm the importance of the key amino acids of the capsid to the antiviral effect of EGCG. Our findings suggest that catechins could act as anti-infective agents against circovirus invasion, as well as provide the basic information for the development and synthesis of structure-based anti-circovirus drugs.

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PMID: 

Int Immunopharmacol. 2010 Dec ;10(12):1505-13. Epub 2010 Sep 15. PMID: 20837172

Abstract Title: 

The influence of donepezil and EGb 761 on the innate immunity of human leukocytes: effect on the NF-κB system.

Abstract: 

Ginkgo biloba special extract EGb 761 and donepezil are drugs used in Alzheimer therapy. The influence of donepezil and EGb 761 on two mechanisms of innate immunity, natural antiviral resistance of human leukocytes ex vivo and NF-κB activation, was studied. Correlation between the innate immunity of leukocytes and NF-κB activation was investigated. The effect of the two drugs on resistance of human leukocytes to vesicular stomatitis virus (VSV) infection was also assessed. Two groups of healthy blood donors (n=30) were distinguished: one with resistant leukocytes (n=15) and one (n=15) with leukocytes sensitive to VSV. The degree of natural resistance of human peripheral blood leukocytes (PBLs) was determined by studying the kinetics of VSV replication. NF-κB activation was assayed by immunocytochemical staining. Efficiency of donepezil and EGb 761 was determined by a special regression model. The toxicity of the preparations to PBLs and the cell lines L(929) and A(549) and their effect on the different viruses was established. Results showed that donepezil used in concentrations of 10-50 μg/ml and EGb761 of 25-100 μg/ml stimulated resistance of human leukocytes. At the same concentrations both preparations decreased activation of transcriptional factor NF-κB. Correlation between innate immunity of PBLs and NF-κB activation was observed. Comparison of the effects of these two drugs showed that EGb 761is more effective in stimulating leukocyte resistance. Donepezil and EGb 761 regulated innate immunity of human leukocytes by stimulating resistance and modulating NF-κB activation. The natural drug was more efficient in stimulating innate antiviral immunity of human leukocytes.

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PMID: 

Antiviral Res. 2008 Jun ;78(3):242-9. Epub 2008 Feb 8. PMID: 18313149

Abstract Title: 

Green tea extract and its major component epigallocatechin gallate inhibits hepatitis B virus in vitro.

Abstract: 

Hepatitis B virus (HBV) infection is endemic in Asia and causes major public health problems worldwide. Present treatment strategies for HBV infections are not satisfactory and the clinical limitation of current antiviral drugs for HBV, such as lamivudine, is causing rapid emergence of drug-resistant viral strains during the prolonged therapeutic treatment. In this research, the efficacy of a natural green tea extract (GTE) against HBV in a stably expressed HBV cell line HepG2-N10 is examined. The expression of viral antigens, HBsAg and HBeAg, were determined by using enzyme linked immuno-absorbent assay (ELISA). Quantitative real-time-PCR (Q-PCR) was used for the determination of extracellular HBV DNA and intracellular replicative intermediates and nuclear covalent closed circular DNA (cccDNA). HBV mRNAs were also analyzed by reverse transcription PCR (RT-PCR). Results showed that the 50% effective concentration (EC50) of GTE on HBsAg, HBeAg, extracellular HBV DNA and intracellular HBV DNA were 5.02, 5.681, 19.81, and 10.76 microg/ml, respectively. While the concentration of GTE with the inhibition percentage of 50% on proliferating cells (CC50) was 171.8 microg/ml. Similar analysis of the principal component of GTE, epigallocatechin gallate (EGCG), revealed it has relative weaker efficacy compared to GTE.

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PMID: 

Molecules. 2015 Mar 19 ;20(3):5137-51. Epub 2015 Mar 19. PMID: 25808155

Abstract Title: 

Antiviral activity of a nanoemulsion of polyprenols from ginkgo leaves against influenza A H3N2 and hepatitis B virus in vitro.

Abstract: 

UNLABELLED: In order to improve the bioavailability levels of polyprenols (derived from ginkgo leaves (GBP)) in the human body, a GBP nanoemulsion was prepared, and its antiviral activity was evaluated against influenza A H3N2 and hepatitis B virus in vitro.METHODS: A GBP nanoemulsion was prepared by inversed-phase emulsification (IPE). Next, we investigated the antiviral activity of the GBP nanoemulsion on influenza A H3N2 and hepatitis B virus in vitro by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenlytetrezolium bromide) method. ELISA and the fluorescent quantitative PCR method were used to measure the content of HBsAg, HBeAg and DNA virus in human samples.RESULTS: The GBP nanoemulsion exhibited uniformity at an average particle size 97 nm with a hydrophilic-lipophilic balance (HLB) of 9.5. GBP is non-toxic to normal cells, hepatitis B virus DNA, hepatitis B virus antigen and HepG2215. Furthermore, GBP could reach a 70% virucidal activity and a 74.9% protection rate (*** p

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PMID: 

Viruses. 2020 Mar 21 ;12(3). Epub 2020 Mar 21. PMID: 32245183

Abstract Title: 

Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway.

Abstract: 

BACKGROUND: Berberine (BBR) is an isoquinoline alkaloid which exhibits a variety of biological and therapeutic properties, and has been reported by some to block replication of the influenza virus. However, contradictory results have also been presented, and the mechanistic explanation is lacking.METHODS: A panel of cell lines (Madin-Darby canine kidney (MDCK), adenocarcinoma human alveolar basal epithelial cells (A549), lung epithelial type I (LET1)) and primary human airway epithelial cells (HAE) susceptible to influenza virus infection were infected with a seasonal influenza A virus in the presence or absence of BBR. Cytotoxicity towards cell lines was measured using XTT assay. The yield of the virus was analyzed using RT-qPCR. To study the molecular mechanism of BBR, confocal microscopy and Western blot analyses of cellular fractions were applied.RESULTS AND CONCLUSIONS: Our results show cell-type-dependent anti-influenza properties of BBR in vitro which suggests that the compound acts on the cell and not the virus. Importantly, BBR hampers influenza replication in primary human airway epithelium 3D cultures that mimic the natural replication site of the virus. Studies show that the influenza A virus upregulates the mitogen-activated protein kinase/extracellular signal-related kinase (MAPK/ERK) pathway and hijacks this pathway for nucleolar export of the viral ribonucleoprotein. Our results suggest that BBR interferes with this process and hampers influenza A replication.

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PMID: 

J Leukoc Biol. 2020 Apr 9. Epub 2020 Apr 9. PMID: 32272506

Abstract Title: 

Berberine suppresses influenza virus-triggered NLRP3 inflammasome activation in macrophages by inducing mitophagy and decreasing mitochondrial ROS.

Abstract: 

Berberine (BBR) is an isoquinoline alkaloid extracted from several commonly used Chinese herbs. Our previous studies demonstrated BBR-mediated alleviation of lung injury due to inflammation and decrease in the mortality of mice with influenza viral pneumonia. The recent argument of autophagy against inflammatory responses has aroused wide concerns. This study focuses on the reactive oxygen species-Nod-like receptor protein 3 (ROS-NLRP3) pathway to investigate whether BBR inhibits NLRP3 inflammasome activation by inducing mitophagy. Our results demonstrate that BBR and mitochondrion-targeted superoxide dismutase mimetic (Mito-TEMPO; a specific mitochondrial ROS scavenger) significantly restricted NLRP3 inflammasome activation, increased mitochondrial membrane potential (MMP), and decreased mitochondrial ROS (mtROS) generation in J774A.1 macrophages infected with PR8 influenza virus. These observations suggest that the inhibitory effects of BBR on NLRP3 inflammasome activation were associated with the amelioration of mtROS generation. BBR treatment induced regular mitophagy, as evident from the increase in microtubule-associated protein 1 light chain 3 II, decrease in p62, colocalization of LC3 and mitochondria, and formation of autophagosomes. However, 3-methyladenine, an autophagy inhibitor, reversed the inhibitory effects of BBR on mitochondrial damage and NLRP3 inflammasome activation in influenza virus-infected macrophages, indicating the involvement of mitophagy in mediating the inhibitory effects of BBR on NLRP3 inflammasome activation. Furthermore, the knockdown of Bcl-2/adenovirus E18-19-kDa interacting protein 3 (BNIP3) expression attenuated the effects of BBR on mitophagy induction to some extent, suggesting that the BBR-induced mitophagy may be, at least in part, mediated in a BNIP3-dependent manner. Similar results were obtained in vivo using a mouse model of influenza viral pneumonia that was administered with BBR. Taken together, these findings suggest that restricting NLRP3 inflammasome activation by decreasing ROS generation through mitophagy induction may be crucial for the BBR-mediated alleviation of influenza virus-induced inflammatory lesions.

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PMID: 

Viruses. 2020 02 29 ;12(3). Epub 2020 Feb 29. PMID: 32121393

Abstract Title: 

Antivirals against Chikungunya Virus: Is the Solution in Nature?

Abstract: 

The worldwide outbreaks of the chikungunya virus (CHIKV) in the last years demonstrated the need for studies to screen antivirals against CHIKV. The virus was first isolated in Tanzania in 1952 and was responsible for outbreaks in Africa and Southwest Asia in subsequent years. Between 2007 and 2014, some cases were documented in Europe and America. The infection is associated with low rates of death; however, it can progress to a chronic disease characterized by severe arthralgias in infected patients. This infection is also associated with Guillain-Barré syndrome. There is no specific antivirus against CHIKV. Treatment of infected patients is palliative and based on analgesics and non-steroidal anti-inflammatory drugs to reduce arthralgias. Several natural molecules have been described as antiviruses against viruses such as dengue, yellow fever,hepatitis C, and influenza. This review aims to summarize the natural compounds that have demonstrated antiviral activity against chikungunya virus in vitro.

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PMID: 

Front Microbiol. 2019 ;10:2367. Epub 2019 Oct 15. PMID: 31681227

Abstract Title: 

Hampering Herpesviruses HHV-1 and HHV-2 Infection by Extract of(EGb) and Its Phytochemical Constituents.

Abstract: 

Despite the availability of several anti-herpesviral agents, it should be emphasized that the need for new inhibitors is highly encouraged due to the increasing resistant viral strains as well as complications linked with periods of recurring viral replication and reactivation of latent herpes infection. Extract of(EGb) is a common phytotherapeutics around the world with health benefits. Limited studies, however, have addressed the potential antiviral activities of EGb, including herpesviruses such as(HHV-1) and(HHV-2). We evaluated the antiviral activity of EGb and its phytochemical constituents: flavonoids and terpenes against HHV-1 and HHV-2. Pretreatment of the herpesviruses with EGb prior to infection of cells produced a remarkable anti-HHV-1 and anti-HHV-2 activity. The extract affected the viruses before adsorption to cell surface at non-cytotoxic concentrations. In this work, through a comprehensive anti-HHV-1 and anti-HHV-2 activity study, it was revealed that flavonoids, especially isorhamnetin, are responsible for the antiviral activity of EGb. Such activity was absent in quercetin and kaempferol. However, EGb showed the most potent antiviral potency compared to isorhamnetin. EGb could augment current therapies for herpes labialis and genital herpes. Moreover, the potential use of EGb in multidrug therapy with synthetic anti-herpes compounds might be considered.

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PMID: 

Molecules. 2016 Oct 20 ;21(10). Epub 2016 Oct 20. PMID: 27775614

Abstract Title: 

Curcumin Shows Antiviral Properties against Norovirus.

Abstract: 

Phytochemicals provide environmentally friendly and relatively inexpensive natural products, which could potentially benefit public health by controlling human norovirus (HuNoV) infection. In this study, 18 different phytochemicals were evaluated for antiviral effects against norovirus using murine norovirus (MNV) as a model for norovirus biology. Among these phytochemicals, curcumin (CCM) was the most potent anti-noroviral phytochemical, followed by resveratrol (RVT). In a cell culture infection model, exposure to CCM or RVT for 3 days reduced infectivity of norovirus by 91% and 80%, respectively. To confirm the antiviral capability of CCM, we further evaluated its antiviral efficacy at various doses (0.25, 0.5, 0.75, 1, and 2 mg/mL) and durations (short-term: 10, 30, 60, and 120 min; long-term: 1, 3, 7, and 14 days). The anti-noroviral effect of CCM was verified to occur in a dose-dependent manner. Additionally, we evaluated the inhibitory effect of each phytochemical on the replication of HuNoV using a HuNoV replicon-bearing cell line (HG23). Neither CCM nor RVT had a strong inhibitory effect on HuNoV replication, which suggests that their antiviral mechanism may involve viral entry or other life cycle stages rather than the replication of viral RNA. Our results demonstrated that CCM may be a promising candidate for development as an anti-noroviral agent to prevent outbreaks of foodborne illness.

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PMID: 

BMC Vet Res. 2017 Oct 10 ;13(1):298. Epub 2017 Oct 10. PMID: 29017487

Abstract Title: 

Curcumin is a promising inhibitor of genotype 2 porcine reproductive and respiratory syndrome virus infection.

Abstract: 

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) could lead to pandemic diseases and huge financial losses to the swine industry worldwide. Curcumin, a natural compound, has been reported to serve as an entry inhibitor of hepatitis C virus, chikungunya virus and vesicular stomatitis virus. In this study, we investigated the potential effect of curcumin on early stages of PRRSV infection.RESULTS: Curcumin inhibited infection of Marc-145 cells and porcine alveolar macrophages (PAMs) by four different genotype 2 PRRSV strains, but had no effect on the levels of major PRRSV receptor proteins on Marc-145 cells and PAMs or on PRRSV binding to Marc-145 cells. However, curcumin did block two steps of the PRRSV infection process: virus internalization and virus-mediated cell fusion.CONCLUSIONS: Our results suggested that an inhibition of genotype 2 PRRSV infection by curcumin is virus strain-independent, and mainly inhibited by virus internalization and cell fusion mediated by virus. Collectively, these results demonstrate that curcumin holds promise as a new anti-PRRSV drug.

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