Tannic acid inhibited norovirus binding to HBGA receptors, a study of 50 Chinese medicinal herbs
ABSTRACT Noroviruses (NoVs) are the leading cause of viral acute gastroenteritis affecting people of all ages worldwide. The disease is difficult to control due to its widespread nature and lack of an antiviral or vaccine. NoV infection relies on the interaction of the viruses with histo-blood group antigens (HBGAs) as host receptors. Here we investigated inhibition effects of Chinese medicinal herbs against NoVs binding to HBGAs for potential antivirals against NoVs. Blocking assays was performed using the NoV protrusion (P) protein as NoV surrogate and saliva as HBGAs. Among 50 clinically effective Chinese medicinal herbs against gastroenteritis diseases, two herbs were found highly effective. Chinese Gall blocked NoV P dimer binding to type A saliva at IC(50)=5.35 μg/ml and to B saliva at IC(50)=21.7 μg/ml. Similarly, Pomegranate blocked binding of NoV P dimer to type A saliva at IC(50)=15.59 μg/ml and B saliva at IC(50)=66.67 μg/ml. Literature data on preliminary biochemistry analysis showed that tannic acid is a common composition in the extracts of the two herbs, so we speculate that it might be the effective compound and further studies using commercially available, highly purified tannic acid confirmed the tannic acid as a strong inhibitor in the binding of NoV P protein to both A and B saliva (IC(50)≈0.1 μM). In addition, we tested different forms of hydrolysable tannins with different alkyl esters, including gallic acid, ethyl gallate, lauryl gallate, octyl gallate and propyl gallate. However, none of these tannins-derivatives revealed detectable inhibiting activities. Our data suggested that tannic acid is a promising candidate antiviral against NoVs.
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ABSTRACT: In this study, the regions in the infectious bursal disease virus (IBDV) genome that are amenable to the introduction of a sequence encoding a virus-neutralizing epitope of Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) protein were identified. By using the reverse genetics approach, insertions or substitutions of sequences encoding the NDV epitope were engineered in the exposed loops (PBC, PHI and PAA') of the VP2 capsid protein and the N terminus of the nonstructural VP5 protein as well as the pep7a and pep7b regions of the pVP2 precursor of a commonly used IBDV vaccine strain, Gt. Three recombinant IBDVs expressing the NDV epitopes were successfully rescued in the PBC, pep7b and VP5 regions and the expressed epitope was recognized by anti-HN antibodies. Genetic analysis showed that the IBDV recombinants carrying the NDV epitopes were stable in cell cultures and in chickens. Animal studies demonstrated that the IBDV recombinants were innocuous in chickens. Vaccination with the recombinant viruses generated antibody responses against both IBDV and NDV, and provided 70-80% protection against IBDV and 50-60% protection against NDV. These results indicate that the recombinant IBDV has the potential to serve as a novel vaccine vector for other pathogens. In future studies, it is worth considering research to improve IBDV vector vaccine to get complete protection and safety of animals and humans.Antiviral research 11/2013; DOI:10.1016/j.antiviral.2013.10.016 · 3.43 Impact Factor
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ABSTRACT: Plant extracts and associated polyphenols are known for their varied health benefits that include antioxidant effects and antimicrobial properties. The increasing consumer demand for cost-effective and natural alternatives to chemically-synthesized antimicrobials and therapeutics that are also sustainable makes the field of phytochemical research rather intriguing and challenging. Human enteric viruses are increasingly recognized worldwide as significant causes of human disease in adults and children, alike. In the absence of available vaccines for the human noroviruses, plant extracts are gaining popularity for the prevention and treatment of viral diseases. Research on plant extracts (particularly polyphenols derived from fruits) for human enteric virus control will be briefly summarized in this article.01/2014; 4C:44-49. DOI:10.1016/j.coviro.2013.12.006
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ABSTRACT: Glioblastoma multiforme (GBM) is one of the most lethal human cancers, accounting for about 15% of all primary brain tumors in adults. Tumor-associated microglia/macrophages (TMMs) are a major constituent of the tumor mass and the tumor microenvironment where they support tumor progression. We previously demonstrated that the NAD + utilizing ectoenzyme CD38 regulates microglia activation and that loss of CD38 inhibits glioma progression and extends the survival of glioma-bearing mice. These results indicated that targeting CD38 in the tumor microenvironment may serve as a novel therapeutic approach to treat glioma. To test this hypothesis, we identified small molecules that inhibit CD38 enzymatic activity (NAD + glycohydrolase): the natural anthranoid rhein, its water-soluble tri-potassium salt (K-rhein), and the polyphenol tannic acid (TA). Microglial properties regulated by CD38 (e.g., NO secretion and LPS/IFNγ activation induced cell death) were inhibited in primary microglia treated with rhein in a CD38-dependent manner. Furthermore, wild-type mice intracranially injected with GL261 mouse glioma cells and intranasally treated with K-rhein or TA, exhibited significant reduction in tumor volume and prolonged lifespan compared to vehicle treated mice. On the other hand, these inhibitors had only a modest effect on tumor-bearing Cd38 −/− mice. Taken together, our results demonstrate that small molecule CD38 inhibitors such as K-rhein and TA can target CD38 in the tumor microenvironment and offer a novel and useful strategy for glioma treatment.