SARS-CoV-2 Entry: At the Crossroads of CD147 and ACE2

Cells. 2021 Jun 8;10(6):1434. doi: 10.3390/cells10061434.

Abstract

In late 2019, the betacoronavirus SARS-CoV-2 was identified as the viral agent responsible for the coronavirus disease 2019 (COVID-19) pandemic. Coronaviruses Spike proteins are responsible for their ability to interact with host membrane receptors and different proteins have been identified as SARS-CoV-2 interactors, among which Angiotensin-converting enzyme 2 (ACE2), and Basigin2/EMMPRIN/CD147 (CD147). CD147 plays an important role in human immunodeficiency virus type 1, hepatitis C virus, hepatitis B virus, Kaposi's sarcoma-associated herpesvirus, and severe acute respiratory syndrome coronavirus infections. In particular, SARS-CoV recognizes the CD147 receptor expressed on the surface of host cells by its nucleocapsid protein binding to cyclophilin A (CyPA), a ligand for CD147. However, the involvement of CD147 in SARS-CoV-2 infection is still debated. Interference with both the function (blocking antibody) and the expression (knock down) of CD147 showed that this receptor partakes in SARS-CoV-2 infection and provided additional clues on the underlying mechanism: CD147 binding to CyPA does not play a role; CD147 regulates ACE2 levels and both receptors are affected by virus infection. Altogether, these findings suggest that CD147 is involved in SARS-CoV-2 tropism and represents a possible therapeutic target to challenge COVID-19.

Keywords: ACE2; CD147; COVID-19; EMMPRIN; SARS-CoV-2; basigin; entry; infection.

MeSH terms

  • A549 Cells
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Angiotensin-Converting Enzyme 2 / physiology*
  • Animals
  • Basigin / antagonists & inhibitors
  • Basigin / genetics
  • Basigin / physiology*
  • COVID-19 / pathology
  • COVID-19 / prevention & control
  • COVID-19 / virology
  • Caco-2 Cells
  • Cell Line
  • Chlorocebus aethiops
  • Hep G2 Cells
  • Host-Pathogen Interactions
  • Humans
  • Molecular Targeted Therapy
  • RNA Interference / physiology
  • RNA, Small Interfering / pharmacology
  • RNA, Small Interfering / therapeutic use
  • Receptors, Virus / metabolism
  • Receptors, Virus / physiology
  • SARS-CoV-2 / metabolism
  • SARS-CoV-2 / physiology*
  • Vero Cells
  • Viral Tropism / physiology
  • Virus Internalization*

Substances

  • BSG protein, human
  • RNA, Small Interfering
  • Receptors, Virus
  • Basigin
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2