SARS-CoV-2 spike protein binding selectively accelerates substrate-specific catalytic activity of ACE2

Area of Science:

• Cardiovascular Science
• Virology
• Biochemistry

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), impacting multiple organ systems.
• COVID-19 patients with cardiovascular disease face higher mortality risks.
• SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as a cellular entry receptor, which is present in cardiac cells.

Purpose of the Study:

• To investigate if SARS-CoV-2 infection alters the enzymatic activity of ACE2.
• To understand the potential link between ACE2 function changes and COVID-19-associated cardiovascular complications.

Main Methods:

• Assessed the effect of SARS-CoV-2 spike protein binding on ACE2 enzymatic activity.
• Utilized substrate analogues for des-Arg9-bradykinin and angiotensin II to measure cleavage rates.

Main Results:

• ACE2 cleavage of des-Arg9-bradykinin substrate analogue was significantly accelerated upon spike protein binding.
• Cleavage of angiotensin II substrate analogue by ACE2 was only minimally affected by spike protein binding.

Conclusions:

• SARS-CoV-2 spike protein binding alters ACE2 enzymatic function, specifically enhancing des-Arg9-bradykinin cleavage.
• These enzymatic alterations may contribute to the pathogenesis of cardiovascular complications observed in COVID-19 patients.