The synthesized (878) compounds were tested for their inhibitory activity on SARS-CoV-2 targets using various assays and X-Ray crystallography. Protease cleavage assays (Nsp5, TMPRSS2, Nsp3) have been performed by the MIT-Broad Foundry to determine activity. Microscale thermophoresis (MST) assays for RdRp (Nsp12 domain), N, and S proteins have been done by Nanotemper GmbH. Details on the assays can be found in Supporting Information Section 4.3.2. In this section, we detail salient experimental issues that were encountered in the assay development, as many (especially the binding assays using MST)