SARS-CoV-2 Spike - ACE2 Binding Assay Service for Inhibitor Screening
The SARS-CoV-2 Spike-ACE2 binding assay for inhibitor screening is performed with surface plasmon resonance (SPR) technology measuring the direct binding of potential therapeutics to the Spike protein RBD (receptor-binding domain) or ACE2. The assay is suitable to determine whether a test molecule(s) inhibits the Spike-ACE2 binding for blocking of SARS-CoV-2 virus entry into host cells.
The SARS-CoV-2 spike-ace2 inhibitor screening assays can investigate two targeting strategies:
1. The development of molecules that occupy the host cell’s ACE2 receptors to block the virus from attaching to the host cell.
2. The development of molecules that bind and saturate the Spike protein on the virus surface such that binding to ACE2 is blocked.
The SPR assay technology allows to:
- Probe the direct binding kinetics (on/off-rate and KD) to optimize target engagement (on-rate) and residence time on the target (off-rate)
- Inhibitor screening of new drug candidates with a throughput of up to 2300 compounds per day.
Our SARS-CoV-2 Spike-ACE2 inhibitor screening service is available for pharmaceutical companies and medical researchers around the world. Read our blog to learn more about the advantages of this assay: Biophysical characterization of compounds disrupting the SARS-CoV-2 Spike – ACE2 interaction using SPR
Spike protein – ACE2 Binding
SARS-CoV-2 is lined with large spike (S) proteins that engage the host cell protein ACE2 (Angiotensin-converting enzyme 2), which serves as a receptor for virus entry. After binding to ACE2, the virus enters the host cell via membrane fusion either with the cell membrane or after endocytosis.
SARS-CoV-2 Spike-ACE2 Inhibitor Screening Assay Details
Surface plasmon resonance for the detection of binding of MLN-4760 to ACE2: In order to directly probe the binding kinetics of small molecules to ACE2, relatively high levels of the target on the sensor chip are needed (due to the large difference in mass between these molecules and the protein target). To achieve these higher levels, ACE2 was covalently attached to the sensor chip via amine coupling. To validate that the target is binding competent once immobilized to the sensor chip, the binding of ACE2 inhibitor MLN-4760 was measured using a kinetic titration (single-cycle kinetics). The KD value of ~1 nM is consistent with the IC50 value of 440 pM.
To learn more about surface plasmon resonance (SPR), please visit our biophysics assays webpage.
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