In conclusion, pharmacologic inhibition of SKI-1/S1P offers a very promising avenue for the development of novel anti-HCV therapeutics (Figure 7) . On one hand, targeting a host cell master molecular switch such as SKI-1/S1P with a novel class of drugs compromising multiple stages of the virus lifecycle would have the main advantage of making it more difficult for the virus to develop escape mutations [86, 88] . On the other hand, the toxicity issues associated with the inhibition of host cell proteases such as SKI-1/ S1P [89] could be addressed by using adjunctive therapy, combining our novel class of lipid-modulating agents with the current standard of care or with the appropriate synergistic directacting antivirals [85, 86] .