To complement traditional antivirals, natural compounds that act via host targets and present high barriers to resistance are of increasing interest. In the work reported here, we detected that homoharringtonine (HHT) presents effective antiviral activity. HHT completely inhibited infections of vesicular stomatitis virus (VSV), Newcastle disease virus (NDV), and porcine epidemic diarrhea virus (PEDV) at concentrations of 50, 100, and 500 nM in cell cultures, respectively. Treatment with HHT at doses of 0.05 or 0.2 mg/kg significantly reduced viral load and relieved severe symptoms in PEDV- or NDV-infected animals. HHT treatment, however, moderately inhibited avian influenza virus (AIV) infection, suggesting its potent antiviral action is restricted to a number of classes of RNA viruses. In this study, we also observed that HHT actively inhibited herpes simplex virus type 1 (HSV-1) replication with a 50% inhibitory concentration (IC₅₀) of 139 nM; the treatment with HHT at 1000 nM led to reductions of three orders of magnitude. Moreover, HHT antagonized the phosphorylation level of endogenous and exogenous eukaryotic initiation factor 4E (p-eIF4E), which might regulate the selective translation of specific messenger RNA (mRNA). HHT provides a starting point for further progress toward the clinical development of broad-spectrum antivirals.

It has been widely known that the Pseudorabies virus (PRV) presents a significant health risk to swine, inflicting considerable economic losses in breeding industry, but those basic function about this disease still keeps unknown. For further understanding its potentiality, the antiviral potential of extracts from five plants against PRV was investigated in vitro. Notably, Aconitum tanguticum and Belamcanda chinensis demonstrated significant inhibition through distinct antiviral mechanisms. Aconitum tanguticum exhibited dose-dependent antiviral activity, significantly reducing viral RNA synthesis, protein expression, and the production of infectious progeny in infected Vero cells. Its primary mechanism involves direct viral binding, leading to substantial reduction in viral titers and a 90% inhibition rate in Vero cells with a concentration of 10 mg/mL. Conversely, Belamcanda chinensis interferes with host cell processes, showing enhanced efficacy post-PRV infection. Both agents effectively protected mice by prolonging survival, alleviating clinical symptoms and histopathological damage in their major organs, and reducing viral loads in lungs and livers. These findings dig out the potential of Aconitum tanguticum and Belamcanda chinensis as therapeutic agents against PRV infections.