Antiviral activity and possible mechanisms of action of pentagalloylglucose (PGG) against influenza A virus

Liu, Ge; Xiong, Sheng; Xiang, Yangfei; Guo, Chaowan; Ge, Feng; Yang, Chong‐Ren; Zhang, Yingjun; Wang, Yifei; Kitazato, Kaio

doi:10.1007/s00705-011-0989-9

Cited by 72 publications

(46 citation statements)

References 40 publications

(35 reference statements)

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“…Pei et al found that autophagy induced following PGG treatment also contributed to its anti-HSV activity (15). PGG can also prevent the adsorption and release of HSV-1 and influenza A virus (18). However, although many antiviral activities of PGG have been explored, more works are required to fully explore the antiviral mechanisms of PGG and to better promote its clinical application.…”

Section: Discussionmentioning

confidence: 99%

“…It exhibits multiple biological activities, including anti-inflammatory (10), anti-mutagenic (11), anti-cancer (12), antioxidant (13), anti-bacterial (14), and antiviral effects. Many studies have reported that PGG can inhibit the replication of HSV-1 (15), respiratory syncytial virus (16), hepatitis B virus (17), and influenza virus (18). The antiviral mechanisms of PGG include direct inactivation, inhibition of virus adsorption on host cells and viral gene expression, as well as protein translational inhibition of the replicated viral genome (15).…”

Section: Introductionmentioning

confidence: 99%

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Pentagalloylglucose Blocks the Nuclear Transport and the Process of Nucleocapsid Egress to Inhibit HSV-1 Infection

Jin

Chen

et al. 2016

Jpn J Infect Dis

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SUMMARY: Herpes simplex virus type 1 (HSV-1), a widespread virus, causes a variety of human viral diseases worldwide. The serious threat of drug-resistance highlights the extreme urgency to develop novel antiviral drugs with different mechanisms of action. Pentagalloylglucose (PGG) is a natural polyphenolic compound with significant anti-HSV activity; however, the mechanisms underlying its antiviral activity need to be defined by further studies. In this study, we found that PGG treatment delays the nuclear transport process of HSV-1 particles by inhibiting the upregulation of dynein (a cellular major motor protein) induced by HSV-1 infection. Furthermore, PGG treatment affects the nucleocapsid egress of HSV-1 by inhibiting the expression and disrupting the cellular localization of pEGFP-UL31 and pEGFP-UL34, which are indispensable for HSV-1 nucleocapsid egress from the nucleus. However, the over-expression of pEGFP-UL31 and pEGFP-UL34 could decrease the antiviral effect of PGG. In this study, for the first time, the antiviral activity of PGG against acyclovir-resistant virus was demonstrated in vitro, and the possible mechanisms of its anti-HSV activities were identified based on the inhibition of nuclear transport and nucleocapsid egress in HSV-1. It was further confirmed that PGG could be a promising candidate for HSV therapy, especially for drug-resistant strains.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pentagalloylglucose Blocks the Nuclear Transport and the Process of Nucleocapsid Egress to Inhibit HSV-1 Infection

Jin

Chen

et al. 2016

Jpn J Infect Dis

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“…As treatment options for hRSV infection are limited, we explored the utility of hRSVpp for identifying cell entry inhibitors that inhibit infection by wild-type hRSV. To this end, we screened selected molecules with known antiviral activity against other enveloped viruses, such as hepatitis C virus (HCV), or against other viruses causing respiratory disease, like influenza A virus (43) or rhinovirus (44). We preincubated hRSV-SH/G/Fpp with increasing concentrations of either the plant-derived flavone BJ486K (Fig.…”

Section: Hrsv-sh -G and -F Proteins Are Incorporated Into Hrsvppmentioning

confidence: 99%

Identification of a Human Respiratory Syncytial Virus Cell Entry Inhibitor by Using a Novel Lentiviral Pseudotype System

Haid

Grethe

Bankwitz

et al. 2016

J Virol

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Lentiviral budding is governed by group-specific antigens (Gag proteins) and proceeds in the absence of cognate viral envelope proteins, which has been exploited to create pseudotypes incorporating envelope proteins from nonlentiviral families. Here, we report the generation of infectious lentiviral pseudoparticles incorporating human respiratory syncytial virus (hRSV) F protein alone (hRSV-Fpp) or carrying SH, G, and F proteins (hRSV-SH/G/Fpp). These particles recapitulate key infection steps of authentic hRSV particles, including utilization of glycosaminoglycans and low-pH-independent cell entry. Moreover, hRSV pseudoparticles (hRSVpp) can faithfully reproduce phenotypic resistance to a small-molecule fusion inhibitor in clinical development (BMS-433771) and a licensed therapeutic F protein-targeting antibody (palivizumab). Inoculation of several human cell lines from lung and liver revealed more than 30-fold differences in susceptibility to hRSVpp infection, suggesting differential expression of hRSV entry cofactors and/or restriction factors between these cell types. Moreover, we observed cell-type-dependent functional differences between hRSVpp carrying solely F protein or SH, G, and F proteins with regard to utilization of glycosaminoglycans. Using hRSVpp, we identified penta-O-galloyl-␤-D-glucose (PGG) as a novel hRSV cell entry inhibitor. Moreover, we show that PGG also inhibits cell entry of hRSVpp carrying F proteins resistant to BMS-433771 or palivizumab. This work sheds new light on the mechanisms of hRSV cell entry, including possible strategies for antiviral intervention. Moreover, hRSVpp should prove valuable to dissect hRSV envelope protein functions, including the interaction with cell entry factors. IMPORTANCELentiviral pseudotypes are highly useful to specifically dissect the functions of viral and host factors in cell entry, which have been exploited for numerous viruses. Here, we successfully created hRSVpp and show that they faithfully recapitulate key characteristics of parental hRSV cell entry. Importantly, hRSVpp accurately mirror hRSV resistance to small-molecule fusion inhibitors and clinically approved therapeutic antibodies. Moreover, we observed highly different susceptibilities of cell lines to hRSVpp infection and also differences between hRSVpp types (with F protein alone or with SH, G, and F proteins) in regard to cell entry. This indicates differential expression of host factors determining hRSV cell entry between these cell lines and highlights the fact that the hRSVpp system is useful to explore the functional properties of hRSV envelope protein combinations. Therefore, this system will be highly useful to study hRSV cell entry and host factor usage and to explore antiviral strategies targeting hRSV cell entry. H uman respiratory syncytial virus (hRSV) is an enveloped, nonsegmented, negative-strand RNA virus classified in the family Paramyxoviridae. It causes upper and lower respiratory tract disease in children and elderly and immunosuppressed persons (1-3). hRSV po...

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“…Cofilin-1 mediates the inhibition of actincytoskeleton remodeling and the anti-HSV activity of pentagalloyl glucose (PGG) [24]. Additionally, we found that PGG also inhibits IAV production by suppressing viral NP accumulation and virion budding on plasma membrane, which may be relevant to actin cytoskeleton remodeling [25]. Therefore, we speculated that cofilin-1 may play a role in IAV assembly and budding.…”

Section: Introductionmentioning

confidence: 98%

Cofilin-1 is involved in regulation of actin reorganization during influenza A virus assembly and budding

Liu

Xiang

Guo

et al. 2014

Biochemical and Biophysical Research Communications

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Influenza A virus (IAV) assembly and budding on host cell surface plasma membrane requires actin cytoskeleton reorganization. The underlying molecular mechanism involving actin reorganization remains unclarified. In this study, we found that the natural antiviral compound petagalloyl glucose (PGG) inhibits F-actin reorganization in the host cell membrane during the late stage of IAV infection, which are associated with the suppression of total cofilin-1 level and its phosphorylation. Knock-down of cofilin-1 reduces viral yields. These findings provide the first evidence that cofilin-1 plays an important role in regulating actin reorganization during IAV assembly and budding.

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Antiviral activity and possible mechanisms of action of pentagalloylglucose (PGG) against influenza A virus

Cited by 72 publications

References 40 publications

Pentagalloylglucose Blocks the Nuclear Transport and the Process of Nucleocapsid Egress to Inhibit HSV-1 Infection

Pentagalloylglucose Blocks the Nuclear Transport and the Process of Nucleocapsid Egress to Inhibit HSV-1 Infection

Identification of a Human Respiratory Syncytial Virus Cell Entry Inhibitor by Using a Novel Lentiviral Pseudotype System

Cofilin-1 is involved in regulation of actin reorganization during influenza A virus assembly and budding

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