Over the last few years, we have had to face several severe virus-mediated disease outbreaks like the current worldwide Sars-CoV-2 pandemic, the Ebola virus outbreak in West Africa and the Zika virus outbreak in South America. The treatment options for virus-mediated diseases are limited, so well-tolerated as well as efficient antiviral therapies are urgently needed. 1 The use of the natural compound silvestrol is a promising new broad-spectrum approach for the treatment of viral infections. Silvestrol can be isolated from the plants of the genus Aglaia 2 and was initially described in the field of cancer research where it showed potent anti-tumour activity in vivo and in vitro. 3-5 The effects of silvestrol are based on the highly specific inhibition of the ATP-dependent DEAD-box RNA helicase eIF4A. 6,7 Several viruses rely on this host factor for the translation of their mRNAs. The targeting of host factors has advantages, like a Abstract Outbreaks of infections with viruses like Sars-CoV-2, Ebola virus and Zika virus lead to major global health and economic problems because of limited treatment options. Therefore, new antiviral drug candidates are urgently needed. The promising new antiviral drug candidate silvestrol effectively inhibited replication of Corona-, Ebola-, Zika-, Picorna-, Hepatis E and Chikungunya viruses. Besides a direct impact on pathogens, modulation of the host immune system provides an additional facet to antiviral drug development because suitable immune modulation can boost innate defence mechanisms against the pathogens. In the present study, silvestrol down-regulated several pro-and anti-inflammatory cytokines (IL-6, IL-8, IL-10, CCL2, CCL18) and increased TNF-α during differentiation and activation of M1-macrophages, suggesting that the effects of silvestrol might cancel each other out. However, silvestrol amplified the anti-inflammatory potential of M2-macrophages by increasing expression of anti-inflammatory surface markers CD206, TREM2 and reducing release of proinflammatory IL-8 and CCL2. The differentiation of dendritic cells in the presence of silvestrol is characterized by down-regulation of several surface markers and cytokines indicating that differentiation is impaired by silvestrol. In conclusion, silvestrol influences the inflammatory status of immune cells depending on the cell type and activation status. K E Y W O R D S antiviral, cytokines, eIF4A, energy metabolism, immune modulation, RNA viruses, rocaglate