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. doi: 10.1016/j.phymed.2020.153296. Epub 2020 Aug 1.

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.

Keywords: Anti-inflammatory; Antiviral; NF-κB; Phillyrin (KD-1); SARS-CoV-2.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antiviral Agents / pharmacology*
  • Betacoronavirus / drug effects*
  • COVID-19
  • Chlorocebus aethiops
  • Coronavirus / drug effects
  • Coronavirus 229E, Human / drug effects*
  • Coronavirus Infections* / metabolism
  • Coronavirus Infections* / virology
  • Cytokines / metabolism
  • Forsythia / chemistry
  • Glucosides / pharmacology*
  • Humans
  • NF-kappa B / metabolism*
  • Pandemics*
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Pneumonia, Viral* / metabolism
  • Pneumonia, Viral* / virology
  • SARS-CoV-2
  • Severe Acute Respiratory Syndrome / virology
  • Signal Transduction / drug effects
  • Vero Cells
  • Virus Replication / drug effects

Substances

  • Anti-Inflammatory Agents
  • Antiviral Agents
  • Cytokines
  • Glucosides
  • NF-kappa B
  • Plant Extracts
  • phillyrin