Viral UL8 Is Involved in the Antiviral Activity of Oleanolic Acid Against HSV-1 Infection

Shan, Tianhao; Ju, Ye; Jia, Jiaoyan; Wang, Zhaoyang; Jiang, Yuzhou; Wang, Yiliang; Zheng, Kai; Ren, Zhe

doi:10.3389/fmicb.2021.689607

Cited by 20 publications

(17 citation statements)

References 44 publications

(51 reference statements)

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“…Oleanolic acid, an essential component of olive oil, exhibits immunomodulatory effects on the human immune system and has been extensively used in cancer prevention by abrogating various signaling pathways ( Ríos, 2010 ). Numerous studies have also illustrated the application of oleanolic acid and ursolic acid as antiviral agents against different viruses ( Khwaza et al, 2018 ; Shan et al, 2021 ). Moreover, silibinin is a flavonolignan known to exhibit anti-neoplastic and antioxidative properties.…”

Section: Discussionmentioning

confidence: 99%

Targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: An in silico investigation

et al. 2023

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The monkeypox virus (MPXV) has become a major threat due to the increasing global caseload and the ongoing multi-country outbreak in non-endemic territories. Due to limited research in this avenue and the lack of intervention strategies, the present study was aimed to virtually screen bioactive phytochemicals against envelope proteins of MPXV via rigorous computational approaches. Molecular docking, molecular dynamic (MD) simulations, and MM/PBSA analysis were used to investigate the binding affinity of 12 phytochemicals against three envelope proteins of MPXV, viz., D13, A26, and H3. Silibinin, oleanolic acid, and ursolic acid were computationally identified as potential phytochemicals that showed strong binding affinity toward all the tested structural proteins of MPXV through molecular docking. The stability of the docked complexes was also confirmed by MD simulations and MM/PBSA calculations. Results from the iMODS server also complemented the findings from molecular docking and MD simulations. ADME analysis also computationally confirmed the drug-like properties of the phytochemicals, thereby asserting their suitability for consumption. Hence, this study envisions the candidature of bioactive phytochemicals as promising inhibitors against the envelope proteins of the MPXV, serving as template molecules that could further be experimentally evaluated for their efficacy against monkeypox.

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Section: Discussionmentioning

confidence: 99%

Targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: An in silico investigation

et al. 2023

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“…Natural products are important antiviral drug resources, and several extracts and pure compounds that have been isolated from plants have been shown to have anti-HSV-1 activity. Natural extracts containing phenols, flavonoids, alkaloids, saponins, steroids, glycosides, and tannins have been found to interfere with the replication of HSV-1 [ 53 , 54 , 55 , 56 , 57 ]. We investigated the antiviral and neuroprotective effects of VBT, a natural product, against HSV-1.…”

Section: Discussionmentioning

confidence: 99%

Vaccinium bracteatum Thunb Extract Inhibits HSV-1 Infection by Regulating ER Stress and Apoptosis

et al. 2022

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Herpes simplex Type 1 (HSV-1) is a neurotropic virus that infects the peripheral and central nervous system. Usually, after primary infection in epithelial cells, HSV-1 migrates retrograde to the peripheral nervous system (PNS), where it establishes a latent infection. HSV-1 can remain latent in the nervous system, and its reactivation in the brain can rarely cause acute HSV-1 encephalitis, often a life-threatening condition, or asymptomatic reactivations that could lead to neuronal damage and ultimately neurodegenerative disorders. Acyclovir and related nucleoside analogs have been used as therapeutic agents for HSV-1 infection, but resistance to the drug can arise, and the protective effect of HSV-1 on brain cells is limited. Therefore, there is an urgent need for research into safe and effective new antiviral agents that can protect brain cells from the damage that is caused by HSV-1 infection. Vaccinium bracteatum Thunb. (VBT) is widely distributed in Korea and China, and has pharmacological actions such as anti-inflammatory, antioxidant, and antidiabetic activity. Studies on the antiviral effect of VBT on HSV-1 infection have not been reported so far. Therefore, we sought to determine the HSV-1 antiviral effect and molecular mechanism of VBT at the cellular level. We confirmed that VBT repressed the VP16 and IE genes in both Vero and SK-N-SH cells. We also found that the generation of HSV-1 virions was inhibited by VBT treatment. VBT inhibited the activities of the HSV-1-induced endoplasmic reticulum (ER) stressors PERK, ATF4, and CHOP. We confirmed that VBT inhibited the activity of apoptosis factors by regulating the expression of death receptor (DR) after HSV-1 infection. As HSV-1 is closely associated with brain diseases, the study of the antiviral drug effects and mechanism of VBT is meaningful. Further studies using animal models of infection will also be performed to determine the potential of VBT as an antiviral agent.

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“…In terms of molecular mechanism, OA demonstrated antiviral activity in the early stages of the HSV infection by suppressing UL8, the critical helicase-primase complex for viral replication. UL8 is a subunit of the helicase-primase heterotrimer that interacts with the other two components, UL5 and UL25, and modulates the formation of the UL5/UL25 subcomplex, leading to viral replication [ 166 ].…”

Section: Oleanolic Acidmentioning

confidence: 99%

Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part I)

Mioc

Milan

Malița

et al. 2022

IJMS

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Triterpenic acids are phytocompounds with a widespread range of biological activities that have been the subject of numerous in vitro and in vivo studies. However, their underlying mechanisms of action in various pathologies are not completely elucidated. The current review aims to summarize the most recent literature, published in the last five years, regarding the mechanism of action of three triterpenic acids (asiatic acid, oleanolic acid, and ursolic acid), corelated with different biological activities such as anticancer, anti-inflammatory, antidiabetic, cardioprotective, neuroprotective, hepatoprotective, and antimicrobial. All three discussed compounds share several mechanisms of action, such as the targeted modulation of the PI3K/AKT, Nrf2, NF-kB, EMT, and JAK/STAT3 signaling pathways, while other mechanisms that proved to only be specific for a part of the triterpenic acids discussed, such as the modulation of Notch, Hippo, and MALAT1/miR-206/PTGS1 signaling pathway, were highlighted as well. This paper stands as the first part in our literature study on the topic, which will be followed by a second part focusing on other triterpenic acids of therapeutic value.

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Viral UL8 Is Involved in the Antiviral Activity of Oleanolic Acid Against HSV-1 Infection

Cited by 20 publications

References 44 publications

Targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: An in silico investigation

Targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: An in silico investigation

Vaccinium bracteatum Thunb Extract Inhibits HSV-1 Infection by Regulating ER Stress and Apoptosis

Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part I)

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