CD147 as a Target for COVID-19 Treatment: Suggested Effects of Azithromycin and Stem Cell Engagement

Stem Cell Rev Rep. 2020 Jun;16(3):434-440. doi: 10.1007/s12015-020-09976-7.

Abstract

The expressive number of deaths and confirmed cases of SARS-CoV-2 call for an urgent demand of effective and available drugs for COVID-19 treatment. CD147, a receptor on host cells, is a novel route for SARS-CoV-2 invasion. Thus, drugs that interfere in the spike protein/CD147 interaction or CD147 expression may inhibit viral invasion and dissemination among other cells, including in progenitor/stem cells. Studies suggest beneficial effects of azithromycin in reducing viral load of hospitalized patients, possibly interfering with ligand/CD147 receptor interactions; however, its possible effects on SARS-CoV-2 invasion has not yet been evaluated. In addition to the possible effect in invasion, azithromycin decreases the expression of some metalloproteinases (downstream to CD147), induces anti-viral responses in primary human bronchial epithelial infected with rhinovirus, decreasing viral replication and release. Moreover, resident lung progenitor/stem are extensively differentiated into myofibroblasts during pulmonary fibrosis, a complication observed in COVID-19 patients. This process, and the possible direct viral invasion of progenitor/stem cells via CD147 or ACE2, could result in the decline of these cellular stocks and failing lung repair. Clinical tests with allogeneic MSCs from healthy individuals are underway to enhance endogenous lung repair and suppress inflammation.

Keywords: Anti-viral responses; Asthma; Basigin; Cellular therapy; Coronavirus; Diabetes mellitus; EMMPRIN; Invasion; Lung stem cells; SARS-CoV-2.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Anti-Bacterial Agents / therapeutic use*
  • Azithromycin / therapeutic use*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / virology
  • Basigin / antagonists & inhibitors
  • Basigin / genetics*
  • Basigin / immunology
  • Betacoronavirus / drug effects*
  • Betacoronavirus / metabolism
  • Betacoronavirus / pathogenicity
  • COVID-19
  • Clinical Trials as Topic
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / immunology
  • Coronavirus Infections / therapy*
  • Coronavirus Infections / virology
  • Gene Expression
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology
  • Humans
  • Lung / immunology
  • Lung / virology
  • Pandemics*
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / immunology
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / therapy*
  • Pneumonia, Viral / virology
  • Protein Binding / drug effects
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / antagonists & inhibitors
  • Spike Glycoprotein, Coronavirus / genetics*
  • Spike Glycoprotein, Coronavirus / immunology
  • Stem Cell Transplantation*
  • Stem Cells / drug effects
  • Stem Cells / immunology
  • Stem Cells / virology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology
  • Viral Load / drug effects

Substances

  • Anti-Bacterial Agents
  • BSG protein, human
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Basigin
  • Azithromycin
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2