Although vaccines and antiviral drugs are available, influenza viruses continue to pose a significant threat to vulnerable populations globally. With the emergence of drug-resistant strains, there is a growing need for novel antiviral therapeutic approaches. We found that 18-hydroxyferruginol (1) and 18-oxoferruginol (2) isolated from Torreya nucifera exhibited strong anti-influenza activity, with 50% inhibitory concentration values of 13.6 and 18.3 μM against H1N1, 12.8 and 10.8 μM against H9N2, and 29.2 μM (only compound 2) against H3N2 in the post-treatment assay, respectively. During the viral replication stages, the two compounds demonstrated stronger inhibition of viral RNA and protein in the late stages (12–18 h) than in the early stages (3–6 h). Moreover, both compounds inhibited PI3K-Akt signaling, which participates in viral replication during the later stages of infection. The ERK signaling pathway is also related to viral replication and was substantially inhibited by the two compounds. In particular, the inhibition of PI3K-Akt signaling by these compounds inhibited viral replication by sabotaging influenza ribonucleoprotein nucleus-to-cytoplasm export. These data indicate that compounds 1 and 2 could potentially reduce viral RNA and viral protein levels by inhibiting the PI3K-Akt signaling pathway. Our results suggest that abietane diterpenoids isolated from T. nucifera may be potent antiviral candidates for new influenza therapies.

Theoretical works by Barnes and Nebel [D. C. Barnes and R. A. Nebel, Phys. Plasmas 5, 2498 (1998); R. A. Nebel and D. C. Barnes, Fusion Technol. 38, 28 (1998)] have suggested that a tiny oscillating ion cloud (referred to as the periodically oscillating plasma sphere or POPS) may undergo a self-similar collapse in a harmonic oscillator potential formed by a uniform electron background. A major uncertainty in this oscillating plasma scheme is the stability of the virtual cathode that forms the harmonic oscillator potential. The electron-electron two-stream stability of the virtual cathode has previously been studied with a fluid model, a slab kinetic model, a spherically symmetric kinetic model, and experimentally [R. A. Nebel and J. M. Finn, Phys. Plasmas 8, 1505 (2001); R. A. Nebel et al., Phys. Plasmas 12, 040501 (2005)]. Here the mode is studied with a two-dimensional particle-in-cell code. Results indicate stability limits near those of the previously spherically symmetric case.

Rotavirus is the main causative agent of viral gastroenteritis among young animals worldwide. Currently, no clinically approved or effective antiviral drugs are available to combat rotavirus infections. Herein, we evaluated the anti-rotaviral activities of extracts and bavachin isolated from Psoralea corylifolia L. (Fabaceae) (P. corylifolia) against the bovine rotavirus G8P[7] and porcine rotavirus G5P[7] in vitro. Two assay strategies were performed: (1) a virucidal assay to reduce viral infectivity by virus neutralization and (2) a post-treatment assay to assess viral replication suppression. The results from the virucidal assay showed that the extracts and bavachin did not exert anti-rotaviral activities. In the follow-up analysis after treatment, bavachin exhibited robust antiviral efficacy, with 50% effective concentration (EC50) values of 10.6 μM (selectivity index [SI] = 2.38) against bovine rotavirus G8P[7] and 13.0 μM (SI = 1.94) against porcine rotavirus G5P[7]. Bavachin strongly suppressed viral RNA synthesis in the early (6 h) and late stages (18 h) after rotaviral infection. These findings strongly suggest that bavachin may have hindered the virions by effectively inhibiting the early stages of the virus replication cycle after rotaviral infection. Furthermore, confocal imaging showed that bavachin suppressed viral protein synthesis, notably that of the rotaviral protein (VP6). These results suggest that bavachin has strong antiviral activity against rotaviruses, inhibits viral replication, and is a candidate natural therapeutic drug targeting rotaviral infection. The utilization of bavachin isolated from P. corylifolia may contribute to decreased mortality rates, lower medication expenses, and enhanced economic viability in domestic farms.

Epigallocatechin 3-O-gallate (EGCG) is a predominant component in green tea with various health benefits. The 67 kDa laminin receptor (67LR) is a nonintegrin cell surface receptor that is overexpressed in various types of cancer; 67LR was identified a cell surface EGCG target that plays a pivotal role in tumor growth, metastasis, and resistance to chemotherapy. However, the plasma concentration of EGCG is limited, and its molecular mechanisms remain unelucidated in colon cancer. In this study, we found that the phosphodiesterase 5 (PDE5) inhibitor, vardenafil (VDN), potentiates EGCG-induced apoptotic cell death in colon cancer cells. The combination of EGCG and VDN induced apoptosis via activation of the endothelial nitric oxide synthase/cyclic guanosine monophosphate/protein kinase Cδ signaling pathway. In conclusion, the PDE5 inhibitor, VDN, may reduce the intracellular PDE5 enzyme activity that potentiates EGCG-induced apoptotic cell death in Caco-2 cells. These results suggest that PDE5 inhibitors can be used to elevate cGMP levels to induce 67LR-mediated, cancer-specific cell death. Therefore, EGCG may be employed as a therapeutic candidate for colon cancer.

Influenza A virus (IAV) remains a major global health threat despite available vaccines and antiviral agents, while current therapies are limited by drug resistance and safety concerns. Curcuminoids exhibit antiviral and anti-inflammatory activities but are constrained by poor water solubility and low bioavailability. To address these limitations, we investigated the antiviral and immunomodulatory properties of a water-solubilized curcuminoid nanoparticle formulation (C–S/M) in both in vitro and in vivo models of IAV infection. To evaluate the potential antiviral and anti-inflammatory effects of C–S/M, we performed a cytopathic effect (CPE) reduction assay in triplicate at 0.001 MOI and quantitative real-time PCR (qRT-PCR) targeting viral NS1 transcripts in MDCK cells. C–S/M suppressed viral NS1 vRNA levels in MDCK cells at lower curcuminoid-equivalent concentrations than native curcuminoids and attenuated IAV-induced TNF-α, IL-6, and IL-8 production. Furthermore, in vivo antiviral efficacy was evaluated in female C57BL/6 mice intranasally infected with IAV and treated orally with C–S/M. Survival, lung viral loads, pulmonary cytokine levels, and splenic immune cell phenotypes were analyzed. In IAV-infected mice, oral administration of C–S/M modestly improved survival and significantly reduced lung viral burden and pulmonary proinflammatory cytokine levels. In addition, in vivo C–S/M treatment was associated with recovery of virus-suppressed T-cell immune responses, including increased Th1 and activated CD8⁺ T cells, reduced regulatory T-cell expansion, and restoration of multifunctional CD4⁺ and CD8⁺ T cells. These findings suggest that C–S/M exerts antiviral and immunomodulatory effects in experimental IAV infection and may serve as a potential adjunctive candidate for further investigation against influenza-associated inflammation.

Background: Influenza A virus (IAV) remains an important respiratory pathogen, and medicinal plants continue to provide chemically diverse sources for antiviral research. Dipsacus asperoides and Phlomis umbrosa have both been used under the traditional name ‘Sokdan’ despite their distinct botanical origins and phytochemical compositions. This study comparatively characterized their chemical profiles and in vitro responses to IAV and used network pharmacology as an exploratory approach to identify candidate pathways for subsequent mechanistic studies. Methods: Ethanolic extracts were evaluated for cytotoxicity in MDCK cells, cytopathic effect (CPE) reduction against IAV A/PR/8/34 (H1N1), and neuraminidase (NA) inhibition. LC-QTOF-MS was used for qualitative chemical profiling, and species-specific compound sets were subjected to target prediction, protein–protein interaction analysis, and pathway enrichment. Results: D. asperoides was non-cytotoxic up to 100 µg/mL and P. umbrosa up to 300 µg/mL under the tested conditions. Both extracts produced modest CPE reduction, reaching maximum inhibition of 21.8 ± 1.4% at 100 µg/mL for D. asperoides and 17.1 ± 6.1% at 200 µg/mL for P. umbrosa, whereas zanamivir (5 µM) produced 76.2 ± 0.8% inhibition. NA inhibition was limited for both extracts. LC-QTOF-MS identified twelve constituents with distinct species-associated detection patterns, including phenylpropanoids, iridoid glycosides, and triterpenoid saponins. Exploratory network analysis identified partially overlapping predicted hubs, including MAPK1/3, RELA, IL-6, TNF, and CASP3, together with additional species-specific nodes. Conclusions: Despite clearly different phytochemical profiles, the two Sokdan species showed a shared pattern of modest in vitro antiviral response. The network pharmacology results should be interpreted as hypothesis-generating rather than mechanistic confirmation and suggest candidate host-response pathways that can guide targeted follow-up experiments. These findings support phytochemical differentiation of the two species while providing a comparative framework for future investigation of their antiviral properties.