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Phillyrin (KD-1) exerts anti-viral and anti-inflammatory activities against novel coronavirus (SARS-CoV-2) and human coronavirus 229E (HCoV-229E) by suppressing the nuclear factor kappa B (NF-κB) signaling pathway.
Phytomedicine. 2020 Nov; 78:153296.P

Abstract

BACKGROUND

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has extensively and rapidly spread in the world, causing an outbreak of acute infectious pneumonia. However, no specific antiviral drugs or vaccines can be used. Phillyrin (KD-1), a representative ingredient of Forsythia suspensa, possesses anti-inflammatory, anti-oxidant, and antiviral activities. However, little is known about the antiviral abilities and mechanism of KD-1 against SARS-CoV-2 and human coronavirus 229E (HCoV-229E).

PURPOSE

The study was designed to investigate the antiviral and anti-inflammatory activities of KD-1 against the novel SARS-CoV-2 and HCoV-229E and its potential effect in regulating host immune response in vitro.

METHODS

The antiviral activities of KD-1 against SARS-CoV-2 and HCoV-229E were assessed in Vero E6 cells using cytopathic effect and plaque-reduction assay. Proinflammatory cytokine expression levels upon infection with SARS-CoV-2 and HCoV-229E infection in Huh-7 cells were measured by real-time quantitative PCR assays. Western blot assay was used to determine the protein expression of nuclear factor kappa B (NF-κB) p65, p-NF-κB p65, IκBα, and p-IκBα in Huh-7 cells, which are the key targets of the NF-κB pathway.

RESULTS

KD-1 could significantly inhibit SARS-CoV-2 and HCoV-229E replication in vitro. KD-1 could also markedly reduce the production of proinflammatory cytokines (TNF-α, IL-6, IL-1β, MCP-1, and IP-10) at the mRNA levels. Moreover, KD-1 could significantly reduce the protein expression of p-NF-κB p65, NF-κB p65, and p-IκBα, while increasing the expression of IκBα in Huh-7 cells.

CONCLUSIONS

KD-1 could significantly inhibit virus proliferation in vitro, the up-regulated expression of proinflammatory cytokines induced by SARS-CoV-2 and HCoV-229E by regulating the activity of the NF-кB signaling pathway. Our findings indicated that KD-1 protected against virus attack and can thus be used as a novel strategy for controlling the coronavirus disease 2019.

Authors+Show Affiliations

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.Kunming University of Science and Technology Library, Kunming, China.State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.Technology Centre, Guangzhou Customs, Guangzhou, China.Technology Centre, Guangzhou Customs, Guangzhou, China.Technology Centre, Guangzhou Customs, Guangzhou, China.Technology Centre, Guangzhou Customs, Guangzhou, China.Technology Centre, Guangzhou Customs, Guangzhou, China.Jilin Yatai Chinese Medicine Development Institute, Changchun, Jilin, China.Jilin Yatai Chinese Medicine Development Institute, Changchun, Jilin, China.State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR, China; KingMed Virology Diagnostic & Translational Center, Guangzhou, China. Electronic address: jeffyah@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32890913

Citation

Ma, Qinhai, et al. "Phillyrin (KD-1) Exerts Anti-viral and Anti-inflammatory Activities Against Novel Coronavirus (SARS-CoV-2) and Human Coronavirus 229E (HCoV-229E) By Suppressing the Nuclear Factor Kappa B (NF-κB) Signaling Pathway." Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 78, 2020, p. 153296.
Ma Q, Li R, Pan W, et al. Phillyrin (KD-1) exerts anti-viral and anti-inflammatory activities against novel coronavirus (SARS-CoV-2) and human coronavirus 229E (HCoV-229E) by suppressing the nuclear factor kappa B (NF-κB) signaling pathway. Phytomedicine. 2020;78:153296.
Ma, Q., Li, R., Pan, W., Huang, W., Liu, B., Xie, Y., Wang, Z., Li, C., Jiang, H., Huang, J., Shi, Y., Dai, J., Zheng, K., Li, X., Hui, M., Fu, L., & Yang, Z. (2020). Phillyrin (KD-1) exerts anti-viral and anti-inflammatory activities against novel coronavirus (SARS-CoV-2) and human coronavirus 229E (HCoV-229E) by suppressing the nuclear factor kappa B (NF-κB) signaling pathway. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 78, 153296. https://doi.org/10.1016/j.phymed.2020.153296
Ma Q, et al. Phillyrin (KD-1) Exerts Anti-viral and Anti-inflammatory Activities Against Novel Coronavirus (SARS-CoV-2) and Human Coronavirus 229E (HCoV-229E) By Suppressing the Nuclear Factor Kappa B (NF-κB) Signaling Pathway. Phytomedicine. 2020;78:153296. PubMed PMID: 32890913.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phillyrin (KD-1) exerts anti-viral and anti-inflammatory activities against novel coronavirus (SARS-CoV-2) and human coronavirus 229E (HCoV-229E) by suppressing the nuclear factor kappa B (NF-κB) signaling pathway. AU - Ma,Qinhai, AU - Li,Runfeng, AU - Pan,Weiqi, AU - Huang,Wenbo, AU - Liu,Bin, AU - Xie,Yuqi, AU - Wang,Zhoulang, AU - Li,Chufang, AU - Jiang,Haiming, AU - Huang,Jicheng, AU - Shi,Yongxia, AU - Dai,Jun, AU - Zheng,Kui, AU - Li,Xiaobo, AU - Hui,Min, AU - Fu,Li, AU - Yang,Zifeng, Y1 - 2020/08/01/ PY - 2020/03/13/received PY - 2020/07/21/revised PY - 2020/07/31/accepted PY - 2020/9/6/pubmed PY - 2020/10/2/medline PY - 2020/9/5/entrez KW - Anti-inflammatory KW - Antiviral KW - NF-κB KW - Phillyrin (KD-1) KW - SARS-CoV-2 SP - 153296 EP - 153296 JF - Phytomedicine : international journal of phytotherapy and phytopharmacology JO - Phytomedicine VL - 78 N2 - BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has extensively and rapidly spread in the world, causing an outbreak of acute infectious pneumonia. However, no specific antiviral drugs or vaccines can be used. Phillyrin (KD-1), a representative ingredient of Forsythia suspensa, possesses anti-inflammatory, anti-oxidant, and antiviral activities. However, little is known about the antiviral abilities and mechanism of KD-1 against SARS-CoV-2 and human coronavirus 229E (HCoV-229E). PURPOSE: The study was designed to investigate the antiviral and anti-inflammatory activities of KD-1 against the novel SARS-CoV-2 and HCoV-229E and its potential effect in regulating host immune response in vitro. METHODS: The antiviral activities of KD-1 against SARS-CoV-2 and HCoV-229E were assessed in Vero E6 cells using cytopathic effect and plaque-reduction assay. Proinflammatory cytokine expression levels upon infection with SARS-CoV-2 and HCoV-229E infection in Huh-7 cells were measured by real-time quantitative PCR assays. Western blot assay was used to determine the protein expression of nuclear factor kappa B (NF-κB) p65, p-NF-κB p65, IκBα, and p-IκBα in Huh-7 cells, which are the key targets of the NF-κB pathway. RESULTS: KD-1 could significantly inhibit SARS-CoV-2 and HCoV-229E replication in vitro. KD-1 could also markedly reduce the production of proinflammatory cytokines (TNF-α, IL-6, IL-1β, MCP-1, and IP-10) at the mRNA levels. Moreover, KD-1 could significantly reduce the protein expression of p-NF-κB p65, NF-κB p65, and p-IκBα, while increasing the expression of IκBα in Huh-7 cells. CONCLUSIONS: KD-1 could significantly inhibit virus proliferation in vitro, the up-regulated expression of proinflammatory cytokines induced by SARS-CoV-2 and HCoV-229E by regulating the activity of the NF-кB signaling pathway. Our findings indicated that KD-1 protected against virus attack and can thus be used as a novel strategy for controlling the coronavirus disease 2019. SN - 1618-095X UR - https://www.unboundmedicine.com/medline/citation/32890913/Phillyrin__KD_1__exerts_anti_viral_and_anti_inflammatory_activities_against_novel_coronavirus__SARS_CoV_2__and_human_coronavirus_229E__HCoV_229E__by_suppressing_the_nuclear_factor_kappa_B__NF_κB__signaling_pathway_ DB - PRIME DP - Unbound Medicine ER -