Severe acute respiratory syndrome coronavirus type 1 (SARS‑CoV‑1) encodes several proteins that modulate host intracellular signaling and regulatory pathways. Among them are nucleocapsid N, membrane M and 3a proteins that directly bind to host targets associated with SARS‑CoV‑1 infection and cytokine production. This Reactome module describes several such binding events and their consequences. First, SARS‑CoV‑1 M binds to 3‑phosphoinositide‑dependent protein kinase 1 (PDPK1) to inhibit PKB/Akt activation (Chan et al. 2007; Tsoi et al. 2014). Second, SARS‑CoV‑1 N binds to SMAD3 to alter transforming growth factor‑β (TGF‑β) signaling (Zhao et al. 2008). This interaction prevents SMAD3 from complexing with SMAD4, thereby blocking TGF-β-sensitized apoptosis. The association of N with SMAD3 also enhances the TGF-β-induced expression of PAI-1 (SERPINE1) promoting tissue fibrosis (Zhao et al. 2008). Third, N protein binding to proteasome subunit p42 (PSMC6) modulates proteasome‑regulated degradation of proteins (Wang et al. 2010). Fourth, SARS‑CoV‑1 N binds SUMO-conjugating enzyme UBC9 (UBE2I) to regulate the activity of UBE2I, affecting downstream signaling factors involved in the cell cycle, in addition to its function in the process of sumoylation (Fan et al. 2006). Finally, binding of viral 3a to the regulator and scaffolding protein caveolin‑1 (CAV1) may regulate virus uptake as well as the trafficking of viral structural proteins (Padhan et al. 2007).