Tannic acid inhibited norovirus binding to HBGA receptors, a study of 50 Chinese medicinal herbs
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, Guangdong, China. Bioorganic & medicinal chemistry
(Impact Factor: 2.79).
02/2012; 20(4):1616-23. DOI: 10.1016/j.bmc.2011.11.040
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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- "Saliva-based NoV-HBGA binding assays were performed as described previously using P dimers of VA387 (GII.4) as NoV surrogates and saliva samples and/or synthetic oligosaccharides as HBGA sources , , . Briefly, synthetic oligosaccharides and/or boiled saliva samples with defined HBGAs phenotype were coated on 96-well microtiter plates, after blocking with nonfat milk, P dimer of VA387 were added. "
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ABSTRACT: Noroviruses (NoVs) are the most important viral pathogens that cause epidemic acute gastroenteritis. NoVs recognize human histo-blood group antigens (HBGAs) as receptors or attachment factors. The elucidation of crystal structures of the HBGA-binding interfaces of a number of human NoVs representing different HBGA binding patterns opens a new strategy for the development of antiviral compounds against NoVs through rational drug design and computer-aided virtual screening methods. In this study, docking simulations and virtual screening were used to identify hit compounds targeting the A and B antigens binding sites on the surface of the capsid P protein of a GII.4 NoV (VA387). Following validation by re-docking of the A and B ligands, these structural models and AutoDock suite of programs were used to screen a large drug-like compound library (derived from ZINC library) for inhibitors blocking GII.4 binding to HBGAs. After screening >2 million compounds using multistage protocol, 160 hit compounds with best predicted binding affinities and representing a number of distinct chemical classes have been selected for subsequent experimental validation. Twenty of the 160 compounds were found to be able to block the VA387 P dimers binding to the A and/or B HBGAs at an IC50<40.0 µM, with top 5 compounds blocking the HBGA binding at an IC50<10.0 µM in both oligosaccharide- and saliva-based blocking assays. Interestingly, 4 of the top-5 compounds shared the basic structure of cyclopenta [a] dimethyl phenanthren, indicating a promising structural template for further improvement by rational design.
PLoS ONE 07/2013; 8(7):e69379. DOI:10.1371/journal.pone.0069379 · 3.23 Impact Factor
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ABSTRACT: Abstract Novel methods to effectively disinfect contact surfaces and prevent human norovirus transmission are essential. The effect of benzalkonium chloride (BAC), potassium peroxymonosulfate (KPMS), tannic acid (TA), and gallic acid (GA) on enteric virus surrogates, murine norovirus (MNV-1), feline calicivirus (FCV-F9), and bacteriophage MS2 was studied. Viruses at high (∼7 log(10) PFU/mL) or low (∼5 log(10) PFU/mL) titers were mixed with equal volumes of BAC (0.2, 0.5, and 1 mg/mL), KPMS (5, 10, and 20 mg/mL), TA (0.02 and 0.2 mg/mL), GA (0.2, 0.4, and 0.8 mg/mL), or water and incubated for 2 h at room temperature. Viral infectivity after triplicate treatments was evaluated using plaque assays in duplicate. Low titers of FCV-F9 and MNV-1 were completely reduced, while low-titer MS2 was reduced by 1.7-1.8 log(10) PFU/mL with BAC at all three concentrations. High-titer FCV-F9 was reduced by 2.87, 3.08, and 3.25 log(10) PFU/mL, and high-titer MNV-1 was reduced by 1.55, 2.32, and 2.75 log(10) PFU/mL with BAC at 0.1, 0.25, and 0.5 mg/mL, respectively. High-titer MS2 was reduced by ∼2 log(10) PFU/mL with BAC at all three concentrations. KPMS at all three concentrations reduced high and low titers of FCV-F9 and MS2 and low-titer MNV-1 to undetectable levels, while high-titer MNV-1 was reduced by 0.92 and 3.44 log(10) PFU/mL with KMPS at 2.5 and 5 mg/mL, respectively. TA at 0.2 mg/mL only reduced high-titer FCV-F9 by 0.98 log(10) PFU/mL and low-titer FCV-F9 by 1.95 log(10) PFU/mL. GA at 0.1, 0.2, and 0.4 mg/mL reduced low-titer FCV-F9 by 2.50, 2.36, and 0.86 log(10) PFU/mL, respectively with negligible effects against high-titer FCV-F9. BAC and KPMS show promise to be used as broad-spectrum contact surface disinfectants for prevention of noroviral surrogate contamination.
Foodborne Pathogens and Disease 08/2012; 9(9):829-34. DOI:10.1089/fpd.2012.1155 · 1.91 Impact Factor
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ABSTRACT: Traditional Chinese herbal medicine (TCHM) is widely used in the prevention and treatment of viral infectious diseases. However, the operative mechanisms of TCHM remain largely obscure, mainly because of its complicated nature and the fragmented nature of research. In recent years, systematic methodologies have been developed to discover the active compounds in TCHM and to elucidate its underlying mechanisms. In this review, we summarize recent progress in TCHM-based antiviral research in China and other Asian countries. In particular, this review focuses on progress in targeting key steps in the viral replication cycle and key cellular components of the host defense system. Recent developments in centralized and standardized TCHM screening and databases are also summarized.
Antiviral research 11/2012; 97(1). DOI:10.1016/j.antiviral.2012.10.006 · 3.94 Impact Factor
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