Antiviral mechanism of carvacrol on HSV-2 infectivity through inhibition of RIP3-mediated programmed cell necrosis pathw
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RESEARCH ARTICLE
Open Access
Antiviral mechanism of carvacrol on HSV-2 infectivity through inhibition of RIP3mediated programmed cell necrosis pathway and ubiquitin-proteasome system in BSC-1 cells Li Wang1†, Dan Wang2†, Xingan Wu3†, Rui Xu1 and Yunlan Li4*
Abstract Background: Carvacrol, as the major components of aromatic plants used for treating human skin diseases including origanum, Satureja, thymus, and coridothymus species, presented a kind of antiviral activity. To explore the mechanisms of carvacrol against herpes simplex virus (HSV) in vitro. Method: The BSC-1 cells model of HSV infection was established, and from the two aspects of viral replication level and cell death pathway, the antiviral effects of carvacrol on HSV infected cells were also evaluated by plaque assay under the three modes including prevention, treatment, and direct inactivation. Results: In the three ways, the half-maximal effective concentration (EC50) of 2% true carvacrol solution on HSV-2 infected cells were severally 0.43, 0.19 and 0.51 mmol/L, and the corresponding therapeutic index (TI) were 4.02, 9.11 and 3.39, respectively. It’s the opposite of the increased levels caused by HSV-2 infection, that both the expressions at the transcription genes and protein levels of virus own replication key factors (including ICP4, ICP27, VP16, gB, and UL30) and cytokines (including RIP3, TNF-α, and MLKL) of infected cells treated with carvacrol were dose-dependently inhibited. Besides, HSV-2 infection can cause the decrease of intracellular protein ubiquitination level, and carvacrol can reverse the ubiquitination decrease level caused by HSV-2 infection. Conclusion: Carvacrol exhibits significant antiviral activity by inhibiting the HSV-2 proliferation process and HSV-2induced TNF-α increasing levels, decreasing RIP3 and MLKL protein expressions through the intracellular RIP3mediated programmed cell necrosis pathway. In addition, carvacrol also may exhibit anti-HSV-2 activity by reversing the ubiquitination decrease level caused by HSV-2 infection on the ubiquitin-proteasome system, which provides insights into the molecular mechanism. Keywords: Carvacrol, Herpes simplex virus-2 (HSV-2), Antiviral activity, Programmed cell necrosis, Ubiquitinproteasome
* Correspondence: [email protected] † Li Wang, Dan Wang and Xingan Wu contributed equally to this work. 4 School of Pharmaceutical Science, Shanxi Medical University, No. 36, Xin Jian South Road, Taiyuan 030001, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicate
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