The anti-HSV-1 effect of quercetin is dependent on the suppression of TLR-3 in Raw 264.7 cells

Lee, Seulki; Lee, Hwan Hee; Shin, Yu Su; Kang, Hyojeung; Cho, Hyosun

doi:10.1007/s12272-017-0898-x

Cited by 59 publications

(40 citation statements)

References 26 publications

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“…C10 and C11 reduced significantly the areas of formed viral plaques when compared to viral controls, and these results could be a consequence of the inhibition of viral release. Several studies have demonstrated the anti-herpes activity of natural products, some of which interfere with early steps [41,42,[56][57][58][59][60][61][62][63][64], while a few affect the last steps of HSV replication [65][66][67][68], as was demonstrated for C10 and C11. For this reason, both cardenolides could be used in combination with other natural products to ensure that different stages of HSV replication would be inhibited, for example with transresveratrol, for which significant anti-HSV activity has also been described [69].…”

Section: Discussionmentioning

confidence: 83%

Elucidation of the mechanism of anti-herpes action of two novel semisynthetic cardenolide derivatives

et al. 2020

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Human herpesviruses are among the most prevalent pathogens worldwide and have become an important public health issue. Recurrent infections and the emergence of resistant viral strains reinforce the need of searching new drugs to treat herpes virus infections. Cardiac glycosides are used clinically to treat cardiovascular disturbances, such as congestive heart failure and atrial arrhythmias. In recent years, they have sparked new interest in their potential anti-herpes action. It has been previously reported by our research group that two new semisynthetic cardenolides, namely C10 (3β-[(N-(2-hydroxyethyl)aminoacetyl] amino-3-deoxydigitoxigenin) and C11 (3β-(hydroxyacetyl)amino-3-deoxydigitoxigenin), exhibited potential anti-HSV-1 and anti-HSV-2 with selectivity index values > 1,000, comparable with those of acyclovir. This work reports the mechanism investigation of anti-herpes action of these derivatives. The results demonstrated that C10 and C11 interfere with the intermediate and final steps of HSV replication, but not with the early stages, since they completely abolished the expression of the UL42 (β) and gD (γ) proteins and partially reduced that of ICP27 (α). Additionally, they were not virucidal and had no prophylactic effects. Both compounds inhibited HSV replication at nanomolar concentrations, but cardenolide C10 was more active than C11 and can be considered as an anti-herpes drug candidate including against acyclovir-resistant HSV-1 strains. AbbreviationsACV acyclovir CC 50 50% cytotoxic concentration CMC carboxymethylcellulose DEX-S dextran sulfate FBS fetal bovine serum HIV human immunodeficiency virus HSV-1 herpes simplex virus type 1 HSV-2 herpes simplex virus type 2 HPV human papillomavirus IC 50 concentration that inhibited 50% of viral replication MEM Eagle's minimum essential medium MOI multiplicity of infection PBS phosphate-buffered saline PFU plaque-forming units SI selectivity index

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Section: Discussionmentioning

confidence: 83%

Elucidation of the mechanism of anti-herpes action of two novel semisynthetic cardenolide derivatives

et al. 2020

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“…Some reports investigated that medicines can affect viruses replication by activating or suppressing TLR3 media apoptosis signaling [11,12], we investigated whether YASML can activate TLR3 to involve in the anti‐PRRSV replication for previous research shown that YASML seemed to induce the activation of apoptotic pathway (Figure 2a,b). So, we knocked down the expression of TLR3 by siRNA.…”

Section: Resultsmentioning

confidence: 99%

Yansuanmalingua inhibits replication of type 2 porcine reproductive and respiratory syndrome virus via activating the caspase‐8 apoptosis pathway

Ding

Cheng³

et al. 2020

J Basic Microbiol

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Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses to the pork industry. The present study showed that Yansuanmalingua (YASML) can inhibit type 2 PRRSV replication using plaque assay, quantitative reverse transcriptase-polymerase chain reaction, and immunofluorescence assay. Furthermore, inhibition of PRRSV replication was shown to be related to Toll-like receptor 3 (TLR3)-dependent apoptosisinduction by YASML in the PRRSV-infected MARC-145, and TLR3-dependent apoptosis-induction by YASML was found to suppress PRRSV replication via the activation of caspase-8 and caspase-3 pathways, respectively. Meanwhile, activation of the caspase-3 pathway seemed to be related to the downregulation of myeloid cell leukemia 1 (Mcl-1) expression. Our results showed that YASML-induced TLR3-dependent apoptosis could be blocked by a pan-caspase inhibitor and small interfering RNA against TLR3. In conclusion, the present study demonstrates that YASML exerts its anti-PRRSV effect by activating the caspase-8/caspase-3 signaling pathway and by negatively regulating Mcl-1 expression. These findings not only provide new insights into the molecular mechanism of YASML inhibition of PRRSV replication via the TLR3-dependent apoptosis pathway but also suggest potential, new antiviral drugs by expressing caspase-3 or down expressing Mcl-1. K E Y W O R D Sapoptosis, caspase-3, caspase-8, siRNA, Toll-like receptor 3, Yansuanmalingua

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“…Furthermore, 51 inhibited the HSV-1-induced nuclear factor (NF)-κB activation through blocking the nuclear translocation and DNA binding of NF-κB. The study of Lee et al [28] gave some insight into the effect of flavonoids, showing the ability of quercetin (19), a "prototype" of flavonoid, to inhibit the expressions of HSV proteins (gD, ICP0) and genes (ICP0, UL13, UL52), and specifically suppress the expression of TLR-3 and inhibit the transcription factors NF-κB and IRF3 [28]. The antiviral activity of halistanol derivatives (96 and 97) against HSV-1 is enabled by the inhibition of viral particles' attachment and penetration; the virucidal effect was also observed.…”

Section: Discussionmentioning

confidence: 99%

Natural Products-Derived Chemicals: Breaking Barriers to Novel Anti-HSV Drug Development

Treml

Gazdová

Šmejkal

et al. 2020

Viruses

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Recently, the problem of viral infection, particularly the infection with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), has dramatically increased and caused a significant challenge to public health due to the rising problem of drug resistance. The antiherpetic drug resistance crisis has been attributed to the overuse of these medications, as well as the lack of new drug development by the pharmaceutical industry due to reduced economic inducements and challenging regulatory requirements. Therefore, the development of novel antiviral drugs against HSV infections would be a step forward in improving global combat against these infections. The incorporation of biologically active natural products into anti-HSV drug development at the clinical level has gained limited attention to date. Thus, the search for new drugs from natural products that could enter clinical practice with lessened resistance, less undesirable effects, and various mechanisms of action is greatly needed to break the barriers to novel antiherpetic drug development, which, in turn, will pave the road towards the efficient and safe treatment of HSV infections. In this review, we aim to provide an up-to-date overview of the recent advances in natural antiherpetic agents. Additionally, this paper covers a large scale of phenolic compounds, alkaloids, terpenoids, polysaccharides, peptides, and other miscellaneous compounds derived from various sources of natural origin (plants, marine organisms, microbial sources, lichen species, insects, and mushrooms) with promising activities against HSV infections; these are in vitro and in vivo studies. This work also highlights bioactive natural products that could be used as templates for the further development of anti-HSV drugs at both animal and clinical levels, along with the potential mechanisms by which these compounds induce anti-HSV properties. Future insights into the development of these molecules as safe and effective natural anti-HSV drugs are also debated.

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The anti-HSV-1 effect of quercetin is dependent on the suppression of TLR-3 in Raw 264.7 cells

Cited by 59 publications

References 26 publications

Elucidation of the mechanism of anti-herpes action of two novel semisynthetic cardenolide derivatives

Elucidation of the mechanism of anti-herpes action of two novel semisynthetic cardenolide derivatives

Yansuanmalingua inhibits replication of type 2 porcine reproductive and respiratory syndrome virus via activating the caspase‐8 apoptosis pathway

Natural Products-Derived Chemicals: Breaking Barriers to Novel Anti-HSV Drug Development

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