Liu Shen capsule shows antiviral and anti-inflammatory abilities against novel coronavirus SARS-CoV-2 via suppression of NF-κB signaling pathway

Pharmacol Res. 2020 Aug:158:104850. doi: 10.1016/j.phrs.2020.104850. Epub 2020 Apr 30.

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread worldwide through person-to-person contact, causing a public health emergency of international concern. At present, there is no specific antiviral treatment recommended for SARS-CoV-2 infection. Liu Shen capsule (LS), a traditional Chinese medicine, has been proven to have a wide spectrum of pharmacological properties, such as anti-inflammatory, antiviral and immunomodulatory activities. However, little is known about the antiviral effect of LS against SARS-CoV-2. Herein, the study was designed to investigate the antiviral activity of SARS-CoV-2 and its potential effect in regulating the host's immune response. The inhibitory effect of LS against SARS-CoV-2 replication in Vero E6 cells was evaluated by using the cytopathic effect (CPE) and plaque reduction assay. The number of virions of SARS-CoV-2 was observed under transmission electron microscope after treatment with LS. Proinflammatory cytokine expression levels upon SARS-CoV-2 infection in Huh-7 cells were measured by real-time quantitative PCR assays. The results showed that LS could significantly inhibit SARS-CoV-2 replication in Vero E6 cells, and reduce the number of virus particles and it could markedly reduce pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-8, CCL-2/MCP-1 and CXCL-10/IP-10) production at the mRNA levels. Moreover, the expression of the key proteins in the NF-κB/MAPK signaling pathway was detected by western blot and it was found that LS could inhibit the expression of p-NF-κB p65, p-IκBα and p-p38 MAPK, while increasing the expression of IκBα. These findings indicate that LS could inhibit SARS-CoV-2 virus infection via downregulating the expression of inflammatory cytokines induced virus and regulating the activity of NF-κB/MAPK signaling pathway in vitro, making its promising candidate treatment for controlling COVID-19 disease.

Keywords: Anti-inflammatory; Antiviral; Liu Shen capsule; SARS-CoV-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives
  • Adenosine Monophosphate / pharmacology
  • Alanine / analogs & derivatives
  • Alanine / pharmacology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antiviral Agents / pharmacology
  • Betacoronavirus / drug effects*
  • COVID-19
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chlorocebus aethiops
  • Complex Mixtures / pharmacology*
  • Coronavirus Infections / virology
  • Humans
  • Inflammation Mediators / metabolism
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism*
  • Pandemics
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Signal Transduction / drug effects*
  • Virion / drug effects

Substances

  • Anti-Inflammatory Agents
  • Antiviral Agents
  • Complex Mixtures
  • Inflammation Mediators
  • Liu-Shen-Wan
  • NF-kappa B
  • remdesivir
  • Adenosine Monophosphate
  • Alanine