Development of an efficient reproducible cell-cell transmission assay for rapid quantification of SARS-CoV-2 Spike interaction with hACE2

We describe herein a novel SARS-CoV-2 cell-cell transmission assay we developed which provides a very rapid and quantitative readout to assess SARS-CoV-2 Spike-hACE2 interaction in the absence of using pseudotyped particles or live virus. We have established two well-behaved stable cell lines which have demonstrated a remarkable correlation with standard cell-free viral pseudotyping for inhibition by convalescent sera, post-vaccine sera, small molecule drugs, and murine anti-spike monoclonal antibodies. The assay is very rapid, reliable, and highly reproducible, without a requirement for any specialized research reagents or laboratory equipment and should be easy to adapt for use in most investigative and clinical settings. It can be effectively used or modified for high throughput screening for compounds and biologics that interfere with virus-cell binding and entry to complement other neutralization assays currently in use.