A bivalent β-carboline derivative inhibits macropinocytosis-dependent entry of pseudorabies virus by targeting the kinase DYRK1A

Wang, Chongyang; Hu, Ruochen; Wang, Ting; Duan, Liuyuan; Hou, Qili; Wang, Junru; Zeng-qi, Yang

doi:10.1016/j.jbc.2023.104605

Cited by 5 publications

(4 citation statements)

References 43 publications

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“…This is consistent with previous reports that the substitution at position N(9) enhances anti-HSV-1 activity [15]. On the other hand, dimers have been shown to exert higher antitumoral activities than monomers on tumoral cell lines [7] and better antiviral properties than monomers against pseudorabies virus (PRV) [31]. Plaque reduction assays confirmed the anti-HSV-1 activity of the dimer, with an EC50 of 9 ± 1 µM (Figure 2C), which is slightly higher than the EC50 previously reported for 9-Me-nHo (4.9 ± 0.4 µM).…”

Section: Discussionsupporting

confidence: 92%

“…Furthermore, several in vitro studies about the potency of different related βC dimers as anticancer agents, showed that a spacer of 4-6 methylene units is needed to achieve a bivalent effect [26]. Also, the anti-PRV activity of several bivalent 9-methyl-harmine compounds, with linkers containing four to eight methylene units, decreases with the prolongation of the linker [31]. Nevertheless, according to our previous studies reporting the antiviral activity of several βCs (particularly 9-Me-nHo) against HSV-1 [15] and the results obtained herein for the dimer, a multifactorial mechanism of action can be suggested.…”

Section: Discussionmentioning

confidence: 99%

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In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex Viruses

Gonzalez,

Vizoso-Pinto,

Erra-Balsells

et al. 2024

IJMS

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Herpes simplex virus (HSV) infections are highly widespread among humans, producing symptoms ranging from ulcerative lesions to severe diseases such as blindness and life-threatening encephalitis. At present, there are no vaccines available, and some existing antiviral treatments can be ineffective or lead to adverse effects. As a result, there is a need for new anti-HSV drugs. In this report, the in vitro anti-HSV effect of 9,9′-norharmane dimer (nHo-dimer), which belongs to the β-carboline (βC) alkaloid family, was evaluated. The dimer exhibited no virucidal properties and did not impede either the attachment or penetration steps of viral particles. The antiviral effect was only exerted under the constant presence of the dimer in the incubation media, and the mechanism of action was found to involve later events of virus infection. Analysis of fluorescence lifetime imaging data showed that the nHo-dimer internalized well into the cells when present in the extracellular incubation medium, with a preferential accumulation into perinuclear organelles including mitochondria. After washing the host cells with fresh medium free of nHo-dimer, the signal decreased, suggesting the partial release of the compound from the cells. This agrees with the observation that the antiviral effect is solely manifested when the alkaloid is consistently present in the incubation media.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex Viruses

Gonzalez,

Vizoso-Pinto,

Erra-Balsells

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…The entry assay was conducted as previously described with some modifications ( Wang et al, 2023b ). Briefly, DF-1 cells were infected with F48E9 (MOI = 10) at 4°C for 1 h to allow viral adsorption.…”

Section: Methodsmentioning

confidence: 99%

“…We found that three 1-formyl- β -carboline derivatives block NDV proliferation through interfering with the viral adsorption and entry processes ( Wang et al, 2021 ). Besides, a bivalent β -carboline derivative inhibits macropinocytosis-dependent entry of pseudorabies virus ( PRV ) by targeting the dual-specificity tyrosine phosphorylation-regulated kinase 1A ( Wang et al, 2023b ). However, the activity and mechanism of canthin-6-one alkaloids inhibiting virus proliferation were rarely studied.…”

Section: Introductionmentioning

confidence: 99%