Development of a SARS-CoV-2-derived receptor-binding domain-based ACE2 biosensor

Area of Science:

• Biochemistry
• Virology
• Molecular Biology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a global health threat.
• The interaction between human angiotensin-converting enzyme 2 (hACE2) and the SARS-CoV-2 receptor-binding domain (RBD) is crucial for viral entry.
• Existing methods lack cellular-level resolution for observing this interaction.

Purpose of the Study:

• To develop a novel biosensor for monitoring hACE2-SARS-CoV-2 RBD interactions.
• To visualize the activity of hACE2-RBD at the single-cell level with high spatiotemporal resolution.

Main Methods:

• Development of a fluorescence resonance energy transfer (FRET)-based hACE2 biosensor.
• Utilizing the biosensor to observe hACE2-RBD activity in real-time at the cellular level.

Main Results:

• The FRET-based biosensor successfully visualized hACE2-RBD interactions with high spatiotemporal resolution.
• The biosensor demonstrated sensitivity to both exogenous and endogenous hACE2 expression.
• The biosensor can be applied in early-stage SARS-CoV-2 infection detection without direct virus use.

Conclusions:

• The novel FRET-based hACE2 biosensor enables real-time monitoring of SARS-CoV-2 infection mechanisms.
• This biosensor offers a potential tool for early detection of SARS-CoV-2 infection.
• The biosensor may facilitate the development of drugs targeting the hACE2-RBD interaction.