ACE2: Evidence of role as entry receptor for SARS-CoV-2 and implications in comorbidities

Area of Science:

• Virology
• Pathogenesis
• Molecular Biology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a disease with a wide range of manifestations and fatal outcomes in vulnerable populations.
• Understanding the viral entry receptor is crucial for comprehending SARS-CoV-2 tropism, transmission, and pathogenesis.
• Angiotensin-converting enzyme 2 (ACE2) was initially identified as the primary entry receptor for SARS-CoV-2.

Purpose of the Study:

• To critically summarize current knowledge on ACE2 function in SARS-CoV-2 infection.
• To highlight limitations and knowledge gaps in fully characterizing ACE2's role.
• To discuss ACE2 expression in comorbidities associated with severe COVID-19 outcomes and explore potential co-receptors and alternative receptors.

Main Methods:

• Literature review and critical analysis of existing research on SARS-CoV-2 entry mechanisms.
• Synthesis of data regarding ACE2 expression, function, and its interaction with viral proteins.
• Discussion of evidence for co-receptors and alternative receptors involved in viral entry.

Main Results:

• ACE2 is a key receptor, but its precise function and regulation in SARS-CoV-2 infection require further elucidation.
• Comorbidities linked to poor COVID-19 outcomes may influence ACE2 expression and function.
• Neuropilins, heparan sulfate, sialic acids, CD147, and GRP78 are being investigated as potential co-factors or alternative entry receptors.

Conclusions:

• Further research is essential to fully understand ACE2's multifaceted role in SARS-CoV-2 pathogenesis.
• Identifying all viral entry factors is critical for developing effective therapeutic strategies against COVID-19.
• Exploring co-receptors and alternative receptors may reveal new targets for antiviral interventions.