Extended Data Fig. 3: Enriched biological pathways and processes of putative antiviral compound targets.

a, Bar graph of enriched biological pathways and putative proteins targeted by the antiviral compounds identified by HTS analysis. Molecular targets contained within enriched GSEA classes, as well as those of the 326 compounds selected for validation, were assessed for enrichment of pathways and biological functions. The x axis corresponds to −log₁₀(P value) while the y axis indicates the enriched terms. The analysis was performed using the online tool Metascape and P values were calculated as indicated in the Methods. b, Chemical epistasis analysis of GPCR agonists and antagonists on viral replication. Vero E6 cells were treated with antagonists of the serotonin receptor 1A (NAD 299 hydrochloride, 5 μM), serotonin receptor 1B (SB-616234-A, 2.5 μM), Dopamine D2 and D3 receptors (elopiprazole, 5 μM) and Platelet-Activating Factor (PAF) receptor (SDZ-62-434, 5 μM) and challenged with SARS-CoV-2. Infection was determined in the top panels as described in Fig. 3. Similarly, Vero E6 cells where pretreated with an agonist of the serotonin receptor 1A (elopiprazole, 5 μM), serotonin receptor 1B (CGS-12066-A maleate, 2.5 μM), Dopamine D2 and D3 receptors (quinelorane hydrochloride, 5 μM) and Platelet-Activating Factor (PAF) receptor (PAF, 5 μM), either alone or in combination (combo) with the corresponding antagonist. Cellular toxicity was measured through enumeration of cell numbers (bottom panels). Data are normalized to the average of DMSO-treated wells and represent mean ± s.e.m. for n = 3 independent experiments.