Figure 8. Schematic inhibition of RSV and HCoV with mTOR inhibitors. Simple illustration is adopted from a previous review 19 . The left portion of the figure delineates the known pathways and interactions between mTORC1 and mTOTC2. ( A ) Rapamycin (Rapa), a mTORC1-specific inhibitor, increases RSV viral protein synthesis and production of viral progenies. Specific inhibition of mTORC1 by Rapamycin deactivates (de-phosphorylation) of S6K1 and S6 (as denoted by the downward blue arrows). This results in negative feed-back activation (phosphorylation) of mTORC2 (red arrow) and an increase in the phosphorylation of Akt (denoted by the upward green arrow). Data supporting this model is presented in Fig. 1. ( B ) Akt inhibitor MK-2206 increases RSV viral proteins and progenies. Inhibition of Akt phosphorylation activates TSC1/2 (red arrow), which deactivates mTORC1 signaling (blue arrows). This decrease of mTORC1 signaling presumably activated mTORC2 (red arrow) in line with the observed activity of rapamycin. Data supporting this model is presented in Fig. 2. ( C ) mTOR inhibitors block essential functions of HCoV OC43 and RSV replication. Inhibition of both mTORC1 and mTORC2 results in decreased phosphorylation of Akt, S6K1 and S6 (blue arrows) ultimately leading to a reduction of protein synthesis and production of progeny virus of RSV (AZD-8055, see Fig. 6) and reduction of viral gene transcription and protein synthesis of human coronavirus OC43 (AZD-8055 and Torin-1, see Fig. 7). Key: ⊢ = inhibition (de-phosphorylation), ► = activation