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Can Host Cell Proteins Like ACE2, ADAM17, TMPRSS2, Androgen Receptor be the Efficient Targets in SARS-CoV-2
Vivek K Gupta1, Madhan K Murthy2, Shripad Patil2
1Department of Biochemistry, ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra-282004, India.
Abstract:
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.
Insights
This review explores how host cell proteases, such as ACE2, ADAM17, and TMPRSS2, and the androgen receptor (AR) facilitate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and infection. Inhibiting these proteins may offer a therapeutic strategy against SARS-CoV-2.
Area of Science:
- Virology
- Molecular Biology
- Pathophysiology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a global pandemic.
- Viral entry into host cells is a critical step for infection, involving virus-host protein interactions.
- Host cell proteases and androgen receptor are implicated in SARS-CoV-2 pathogenesis.
Purpose of the Study:
- To review the role of host cell proteases (ACE2, ADAM17, TMPRSS2) and androgen receptor (AR) in SARS-CoV-2 infection.
- To elucidate how these host factors contribute to viral spread and disease severity.
- To explore the potential of inhibiting these host proteins as a therapeutic approach.
Main Methods:
- Literature review of published articles, including reviews, research papers, preprints, and official documents.
- Analysis of physiological aspects relevant to SARS-CoV and SARS-CoV-2.
- Synthesis of existing data to hypothesize the roles of specific host proteins.
Main Results:
- ACE2, ADAM17, and TMPRSS2 are key proteases involved in SARS-CoV-2 entry.
- Androgen receptor (AR) also plays a significant role in SARS-CoV-2 infection.
- These host proteins enhance viral pathology and infectivity.
Conclusions:
- Host cell proteases and androgen receptor are crucial for SARS-CoV-2 infection.
- Targeting these host proteins presents a potential therapeutic avenue for preventing or treating SARS-CoV-2 infections.
- Further research into these host-pathogen interactions is warranted.
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