Can Host Cell Proteins Like ACE2, ADAM17, TMPRSS2, Androgen Receptor be the Efficient Targets in SARS-CoV-2 Infection?

Curr Drug Targets. 2021;22(10):1149-1157. doi: 10.2174/1389450121999201125201112.


A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV- -2), which caused a large disease outbreak in Wuhan, China in December 2019, is currently spreading across the world. Along with binding of the virus spike with the host cell receptor, fusion of the viral envelope with host cell membranes is a critical step in establishing successful infection of SARS-CoV-2. In this entry process, a diversity of host cell proteases and androgen receptor play a very important role directly or indirectly. These features of SARS-CoV-2 entry contribute to its rapid spread and severe symptoms, high fatality rates among infected patients. This review is based on the latest published literature including review articles, research articles, hypothetical manuscript, preprint articles and official documents. The literature search was made from various published papers on physiological aspects relevant to SARS-CoV and SARS-CoV-2. In this report, we focus on the role of host cell proteases (ACE2, ADAM17, TMPRSS2) and androgen receptor (AR) in SARS-CoV-2 infection. The hypotheses put forth by us are based on the role played by the proteases ACE2, ADAM17, TMPRSS2 and AR in SARS-CoV-2 infection, which were deduced based on various studies. We have also summarized how these host proteins increase the pathology and the infective ability of SARS-CoV-2 and we posit that their inhibition may be a therapeutic option for preventing SARS-CoV-2 infection.

Keywords: ACE2; ADAM17; Androgen receptor; COVID-19; SARS-CoV-2; TMPRSS2; anti-viral drugs..

Publication types

  • Review

MeSH terms

  • ADAM17 Protein / metabolism
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Biomarkers / metabolism*
  • COVID-19 / drug therapy
  • COVID-19 / metabolism*
  • Humans
  • Molecular Targeted Therapy
  • Receptors, Androgen / metabolism
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / pathogenicity
  • SARS-CoV-2 / physiology*
  • Serine Endopeptidases / metabolism
  • Virus Internalization / drug effects


  • AR protein, human
  • Antiviral Agents
  • Biomarkers
  • Receptors, Androgen
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human
  • ADAM17 Protein
  • ADAM17 protein, human