Is targeting angiotensin-converting enzyme 2 (ACE2) a prophylactic strategy against COVID-19?

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• COVID-19 prevention is crucial for vulnerable groups at high risk of severe illness.
• Current strategies like vaccines and neutralizing antibodies face challenges due to SARS-CoV-2 mutations.
• Angiotensin-converting enzyme 2 (ACE2) is the primary receptor for SARS-CoV-2 entry into human cells.

Purpose of the Study:

• To explore the potential of reducing ACE2 expression as a novel prophylactic strategy against COVID-19.
• To evaluate the implications of ACE2 downregulation on SARS-CoV-2 susceptibility.
• To consider the balance between prophylactic benefits and potential risks associated with ACE2 modulation.

Main Methods:

• Review of in vitro, in vivo, and ex situ studies on ACE2 expression and SARS-CoV-2 infection.
• Analysis of the physiological roles of ACE2.
• Consideration of future prophylactic strategies including vaccine updates and decoy receptors.

Main Results:

• Downregulation of ACE2 was shown to decrease susceptibility to SARS-CoV-2 infection across multiple experimental models.
• ACE2 plays essential physiological roles, necessitating careful consideration of risks versus benefits.
• SARS-CoV-2's continuous mutation necessitates adaptive prophylactic measures.

Conclusions:

• Reducing ACE2 expression presents a potential avenue for COVID-19 prophylaxis, requiring clinical validation.
• Careful risk-benefit assessment is essential due to ACE2's physiological functions.
• Future strategies may involve updated vaccines and soluble ACE2 decoy receptors to combat viral evolution.