Analysis of the molecular mechanism of Pudilan (PDL) treatment for COVID-19 by network pharmacology tools

Biomed Pharmacother. 2020 Aug:128:110316. doi: 10.1016/j.biopha.2020.110316. Epub 2020 May 30.

Abstract

Background: Pudilan (PDL), a four-herb prescription with the traditional function of heat-clearing and detoxifying, has been clinically used as an anti-SARS-CoV-2 infectory agent in China. PDL might also have therapeutic potentials for COVID-19 while the underlying mechanisms remain to be clarified.

Methods: We used network pharmacology analysis and selected 68 co-targeted genes/proteins as targets of both PDL and COVID-19. These co-targeted genes/proteins were predicted by SwissDock Server for their high-precision docking simulation, and analyzed by STRING for proteins to protein interaction (PPI), pathway and GO (gene ontology) enrichment. The therapeutic effect for PDL treatment on COVID-19 was validated by the TCMATCOV (TCM Anti COVID-19) platform.

Results: PDL might prevent the entrance of SARS-CoV-2 entry into cells by blocking the angiotensin-converting enzyme 2 (ACE2). It might inhibit the cytokine storm by affecting C-reactive protein (CRP), interferon-γ (IFN-γ), interleukin- 6 (IL-6), interleukin- 10 (IL-10), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), C-C motif chemokine ligand 5 (CCL5), transforming growth factor-β1 (TGFβ1), and other proteins. PDL might moderate the immune system to shorten the course of the disease, delay disease progression, and reduce the mortality rate.

Conclusion: PDL might have a therapeutic effect on COVID-19 through three aspects, including the moderate immune system, anti-inflammation, and anti-virus entry into cells.

Keywords: COVID-19; Network pharmacology; SARS-CoV-2 infection; Targeted therapy; Traditional Chinese herbs.

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Anti-Inflammatory Agents / pharmacology
  • Antiviral Agents / pharmacology*
  • Betacoronavirus* / drug effects
  • Betacoronavirus* / isolation & purification
  • COVID-19
  • Coronavirus Infections* / drug therapy
  • Coronavirus Infections* / immunology
  • Cytokine Release Syndrome* / drug therapy
  • Cytokine Release Syndrome* / immunology
  • Drugs, Chinese Herbal / pharmacology*
  • Humans
  • Immunologic Factors / pharmacology
  • Interferon-gamma / immunology
  • Interleukins / immunology
  • Molecular Docking Simulation
  • Pandemics*
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral* / drug therapy
  • Pneumonia, Viral* / immunology
  • Protein Interaction Maps
  • SARS-CoV-2
  • Transforming Growth Factor beta / immunology
  • Virus Internalization / drug effects*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Anti-Inflammatory Agents
  • Antiviral Agents
  • Drugs, Chinese Herbal
  • Immunologic Factors
  • Interleukins
  • Pudilan xiaoyan
  • Transforming Growth Factor beta
  • Interferon-gamma
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2