Microscale thermophoresis emerged as a high-throughput label-free method to evaluate binding constants and is extensively used in the pharmaceutical industry and in CROs. Therefore, this method was used for the three protein targets without protease activity, i.e., S, RdRp (Nsp12 domain), and N. Various constructs of whole-length or subdomains of the targets are available from commercial sources. In this section, we will describe the assay development, the choice of positive controls (that are absolutely needed for MST), and binding outcomes.