The pandemic coronavirus disease 2019 () is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The Spike glycoprotein is expressed on the surface of the virus as a trimer. Each Spike protein consists of two subunits, S1 and S2, and the S1 subunit has a receptor binding domain (RBD) which recognizes and attaches to the Angiotensin-Converting Enzyme 2 (ACE2) receptor found on the surface of type I and II pneumocytes, endothelial cells, and ciliated bronchial epithelial cells. Drugs targeting the interaction between the Spike protein of SARS-CoV-2 and ACE2 may offer some protection against the viral infection. The SARS-CoV-2 Spike Trimer (S1+S2) :ACE2 Inhibitor Screening Assay Kit includes the Spike protein in its native trimeric conformation to provide a more physiologically relevant screen for inhibitors of the Spike S1:ACE2 interaction.The SARS-CoV-2 Spike Trimer (S1+S2) :ACE2 Inhibitor Screening Assay Kit is designed for screening and profiling inhibitors of this interaction. The key to this kit is that the SARS-CoV-2 Spike Trimer (S1+S2) protein provides a more biologically relevant model than monomeric Spike RBD protein for the investigation of SARS-CoV-2/host cell interaction. Only a few simple steps on a microtiter plate are required for the assay. First, SARS-CoV-2 Spike Trimer (S1+S2) is coated on a 96-well plate. Next, Biotin-ACE2 is incubated with SARS-CoV-2 Spike Trimer (S1+S2) on the plate. Finally, the plate is treated with Streptavidin-HRP followed by addition of a colorimetric HRP substrate to produce color, which then can be quenched and measured using a UV/Vis microplate reader.