Vaccines for the COVID-19 pandemic are limited and so effective drugs are needed. The binding affinity of several SARS-CoV-2 variants to human ACE2 receptors was measured using a frequency-locked optical whispering evanescent resonator (FLOWER) system. The advantage of FLOWER is that it is label-free and so drug candidates do not need to be labeled and it is ultra-sensitive so drugs over a wide range of binding affinities can be tested. The dissociation equilibrium constants of spike-RBD wild type as well as two variants, were analyzed and compared. Several drug candidates which inhibit the spike-RBD binding to ACE2, predicted by in-silico simulation, were screened using a competitive binding assay and the corresponding inhibitor constants were measured.
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