Poly (4-styrenesulfonic acid-co-maleic acid) is an entry inhibitor against both HIV-1 and HSV infections – Potential as a dual functional microbicide

Qiu, Min; Chen, Yu; Song, Siwei; Song, Hui; Chu, Ying; Yuan, Zhongping; Cheng, Lin; Zheng, Datong; Chen, Zhiwei; Wu, Zhiwei

doi:10.1016/j.antiviral.2012.08.005

Cited by 17 publications

(18 citation statements)

References 55 publications

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“…It was observed that Kuwanon X had no virucidal effect on HSV-1, but could suppress viral attachment and penetration. Previous research have shown that most inhibitors of viral penetration are mainly biopolymers, such as sulfated polysaccharides, 25) poly(4-styrenesulfonic acid-comaleic acid), 33) and SP-303, 34) while Kuwanon X is a low molecular weight monomeric compound. So the inhibitory effect of Kuwanon X on HSV-1 penetration was further confirmed by confocal laser scan microscope assay (Fig.…”

Section: Discussionmentioning

confidence: 99%

Anti-HSV Activity of Kuwanon X from Mulberry Leaves with Genes Expression Inhibitory and HSV-1 Induced NF-κB Deactivated Properties

Shen

Zhang

et al. 2016

Biological & Pharmaceutical Bulletin

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Six stilbene derivatives isolated from Mulberry leaves including Kuwanon X, Mulberrofuran C, Mulberrofuran G, Moracin C, Moracin M 3′-O-b-glucopyranoside and Moracin M were found to have antiviral effects against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) at different potencies except for Mulberrofuran G. Kuwanon X exhibited the greatest activity against HSV-1 15577 and clinical strains and HSV-2 strain 333 with IC 50 values of 2.2, 1.5 and 2.5 µg/mL, respectively. Further study revealed that Kuwanon X did not inactivate cell-free HSV-1 particles, but inhibited cellular adsorption and penetration of HSV-1 viral particles. Following viral penetration, Kuwanon X reduced the expression of HSV-1 IE and L genes, and decreased the synthesis of HSV-1 DNA. Furthermore, it was demonstrated that Kuwanon X inhibited the HSV-1-induced nuclear factor (NF)-κB activation through blocking the nuclear translocation and DNA binding of NF-κB. These results suggest that Kuwanon X exerts anti-HSV activity through multiple modes and could be a potential candidate for the therapy of HSV infection.Key words anti-herpes simplex virus (HSV) activity; Kuwanon X; penetration; gene expression; nuclear factor (NF)-κB; Mulberry Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are prevalent pathogens worldwide. HSV-1 is the main cause of orofacial herpes, cephalitis, corneal blindness, and several disorders of the peripheral nervous system; HSV-2 is usually associated with recurrent genital herpes, meningoencephalitis in neonates and meningitis in adults. Both HSV-1 and HSV-2 can cause latent infections in the neurons system, and then cause lesions at or near the point of entry into the body when they are reactivated.1,2) Recently, it was reported that HSV infections can increase the transmission of human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1).3) During the productive infection, a successful HSV replication cycle is dependent on the completion of several steps, including α (immediate-early or IE), β (early or E), γ (late or L) genes and unpaired DNA replication based on sequential expression. The IE genes, such as UL54, encode transacting regulators of gene expression. The E genes, including UL52, are involved in viral DNA synthesis and nucleotide metabolism. The L genes, mainly encode structural proteins, e.g. ICP5 encoding the main capsid protein VP5. 4)The standard therapy for HSV infections are nucleoside analogues, such as acyclovir (ACV) and penciclovir. However, the emergence of HSV strains resistant to ACV remains an important clinical concern in immunocompromised individuals.5) Therefore, it is necessary to develop new antiherpetic agents with mechanisms of action different from that of nucleoside analogues.Mulberry (Morusalba L.) is widely cultivated in several Asian countries. Its leaves, fruits, twigs and root barks have long been used in Chinese medicine to reduce fever, maintain liver health, improve eyesight and lower blood pressure. Besides, Mulberry leaf is commonly...

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Section: Discussionmentioning

confidence: 99%

Anti-HSV Activity of Kuwanon X from Mulberry Leaves with Genes Expression Inhibitory and HSV-1 Induced NF-κB Deactivated Properties

Shen

Zhang

et al. 2016

Biological & Pharmaceutical Bulletin

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“…Nuclear and cytoplasmic total proteins were separated and extracted using a commercial kit. Western blot was performed as previously described [21] .…”

Section: Western Blot and In-cell Westernmentioning

confidence: 99%

“…In-cell Western assay was conducted according to our published protocols [21] . Briefly, the cell monolayers were fixed with 4% paraformaldehyde for 20 min and permeabilized by 5 washes with 0.1% Triton X-100 in PBS.…”

Section: Western Blot and In-cell Westernmentioning

confidence: 99%

BX-795 inhibits HSV-1 and HSV-2 replication by blocking the JNK/p38 pathways without interfering with PDK1 activity in host cells

Su¹,

Qiu²,

Li³

et al. 2017

Acta Pharmacol Sin

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BX-795 is an inhibitor of 3-phosphoinositide-dependent kinase 1 (PDK1), but also a potent inhibitor of the IKK-related kinase, TANKbinding kinase 1 (TBK1) and IKKε. In this study we attempted to elucidate the molecular mechanism(s) underlying the inhibition of BX-795 on Herpes simplex virus (HSV) replication. HEC-1-A or Vero cells were treated with BX-795 and infected with HSV-1 or HSV-2 for different periods. BX-795 (3.125-25 µmol/L) dose-dependently suppressed HSV-2 replication, and displayed a low cytotoxicity to the host cells. BX-795 treatment dose-dependently suppressed the expression of two HSV immediate-early (IE) genes (ICP0 and ICP27) and the late gene (gD) at 12 h postinfection. HSV-2 infection resulted in the activation of PI3K and Akt in the host cells, and BX-795 treatment inhibited HSV-2-induced Akt phosphorylation and activation. However, the blockage of PI3K/Akt/mTOR with LY294002 and rapamycin did not affect HSV-2 replication. HSV-2 infection increased the phosphorylation of JNK and p38, and reduced ERK phosphorylation at 8 h postinfection in the host cells; BX-795 treatment inhibited HSV-2-induced activation of JNK and p38 MAP kinase as well as the phosphorylation of c-Jun and ATF-2, the downstream targets of JNK and p38 MAP kinase. Furthermore, SB203580 (a p38 inhibitor) or SP600125 (a JNK inhibitor) dose-dependently inhibited the viral replication in the host cells, whereas PD98059 (an ERK inhibitor) was not effective. Moreover, BX-795 blocked PMA-stimulated c-Jun activation as well as HSV-2-mediated c-Jun nuclear translocation. BX-795 dose-dependently inhibited HSV-2, PMA, TNF-α-stimulated AP-1 activation, but not HSV-induced NF-κB activation. Overexpression of p38/JNK attenuated the inhibitory effect of BX-795 on HSV replication. BX-795 completely blocked HSV-2-induced MKK4 phosphorylation, suggesting that BX-795 acting upstream of JNK and p38 MAP kinase. In conclusion, this study identifies the anti-HSV activity of BX-795 and its targeting of the JNK/p38 MAP kinase pathways in host cells.

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“…Briefly, cells were detached by phosphate-buffered saline (PBS) containing 0.02 % ethylenediaminetetraacetic acid (EDTA; Sigma Aldrich). Subsequently, 2.5x10 5 …”

Section: Binding Of Cooh-terminal Peptides To Cellular Gags and Compementioning

confidence: 99%

“…Previously, antiviral drugs targeting the binding and entry of viruses such as human immunodeficiency virus (HIV), hepatitis C virus (HCV) and herpes simplex viruses type 1 and 2 (HSV-1 and -2) were developed and approved or are currently undergoing clinical trials [3][4][5]. Blocking the viral infection at this early stage is less toxic with less side effects compared to chemotherapeutics affecting the viral multiplication cycle that are currently used.…”

Section: Introductionmentioning

confidence: 99%

Basic chemokine-derived glycosaminoglycan binding peptides exert antiviral properties against dengue virus serotype 2, herpes simplex virus-1 and respiratory syncytial virus

Vanheule

Vervaeke

Mortier

et al. 2016

Biochemical Pharmacology

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Chemokines attract leukocytes to sites of infection in a G protein-coupled receptor (GPCR) and glycosaminoglycan (GAG) dependent manner. Therefore, chemokines are crucial molecules for proper functioning of our antimicrobial defense mechanisms. In addition, some chemokines have GPCRindependent defensin-like antimicrobial activities against bacteria and fungi. Recently, high affinity for GAGs has been reported for the positively charged COOH-terminal region of the chemokine CXCL9. In addition to CXCL9, also CXCL12γ has such a positively charged COOH-terminal region with about 50 % positively charged amino acids. In this report, we compared the affinity of COOH-terminal peptides of These short chemokine-derived peptides may be lead molecules for the development of novel antiviral agents.

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Poly (4-styrenesulfonic acid-co-maleic acid) is an entry inhibitor against both HIV-1 and HSV infections – Potential as a dual functional microbicide

Cited by 17 publications

References 55 publications

Anti-HSV Activity of Kuwanon X from Mulberry Leaves with Genes Expression Inhibitory and HSV-1 Induced NF-κB Deactivated Properties

Anti-HSV Activity of Kuwanon X from Mulberry Leaves with Genes Expression Inhibitory and HSV-1 Induced NF-κB Deactivated Properties

BX-795 inhibits HSV-1 and HSV-2 replication by blocking the JNK/p38 pathways without interfering with PDK1 activity in host cells

Basic chemokine-derived glycosaminoglycan binding peptides exert antiviral properties against dengue virus serotype 2, herpes simplex virus-1 and respiratory syncytial virus

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