A plant-derived compound called ailanthone reduced HSV-1 replication in several cell models and eased corneal disease in a mouse model of herpes simplex keratitis, according to the study. The researchers found that ailanthone acted mainly after the virus entered cells and linked much of this effect to reduced expression of integrin beta 2, or ITGB2, a host protein that supports viral replication. The results identify ailanthone as a potential drug candidate, but the experiments do not establish that it is safe or effective in people.

The team began by screening natural compounds and testing ailanthone in African green monkey kidney Vero cells infected with HSV-1. Concentrations of 100 to 3,000 nanomolar reduced transcription of the viral immediate-early genes ICP0 and ICP4 and the late gene gD in a dose-dependent manner. The compound also reduced plaque formation and the concentration of progeny virus released into culture. Ailanthone had a half-maximal cytotoxic concentration above 10,000 nanomolar in these cells, while its half-maximal effective concentration against viral replication was 197.4 nanomolar, giving a selectivity index greater than 50. It also suppressed HSV-1-induced increases in the inflammatory cytokine genes IL-1B and TNF-α.

Antiviral activity was subsequently observed in human corneal epithelial cells, a model more directly relevant to the tissue affected by keratitis. Ailanthone concentrations of 100 to 500 nanomolar markedly reduced the cytopathic effects of HSV-1F, lowered expression of ICP0, ICP4 and gD, and reduced the viral induction of IL-1B and TNF-α. Its effective concentration in these cells was 50.16 nanomolar, with a cytotoxicity concentration above 10,000 nanomolar and a selectivity index greater than 100. The researchers also tested the compound in human retinal pigment epithelial ARPE-19 cells, where it reduced viral gene expression, plaque formation and progeny-virus titers while showing low cytotoxicity.

Activity was not restricted to the laboratory HSV-1F strain. In ARPE-19 cells, ailanthone concentration-dependently inhibited the late gD gene in the clinical acyclovir-resistant strain HSV-1/153, whereas 1,000 nanomolar acyclovir had little effect. The compound’s effective concentration was 35.05 nanomolar against HSV-1F and 227.4 nanomolar against HSV-1/153, with selectivity indices above 100 for both strains. A time-of-addition experiment indicated that ailanthone did not prevent attachment of HSV-1 to cells. It reduced entry under one experimental schedule and had its strongest effect on post-entry replication, where it lowered gD expression.

To investigate how the compound might work, the researchers combined computational target prediction with protein-interaction network analysis. They identified 36 targets shared by ailanthone and herpes simplex keratitis, then selected ITGB2 as a highly connected hub in the resulting network and as a top candidate in molecular docking. The predicted docking score for ailanthone and ITGB2 was −8.6 kcal per mole. Computational predictions alone cannot establish direct binding, so the team also performed a drug affinity responsive target stability assay in THP-1 cell lysates. Ailanthone protected ITGB2 from digestion by the protease pronase E in a dose-dependent manner, while acyclovir did not, providing biochemical evidence consistent with a direct interaction.

Functional experiments then tested whether ITGB2 was necessary for the antiviral effect. Three independent small interfering RNAs reduced ITGB2 messenger RNA and protein in THP-1 cells. Following HSV-1 infection, this knockdown lowered gD messenger RNA and protein and reduced the number of plaques produced when culture supernatants were transferred to fresh Vero cells. The converse pattern appeared when ITGB2 was overexpressed: elevated ITGB2 increased gD expression in infected cells, and it partially counteracted the reduction in gD protein caused by ailanthone in 293T and ARPE-19 cells. Together, these loss- and gain-of-function results support the conclusion that ailanthone’s antiviral activity is mediated at least partly by lowering ITGB2.

The researchers next tested ailanthone in an acute mouse model of HSV-1 keratitis. Six-week-old male BALB/c mice received a corneal scratch followed by application of HSV-1F, then received intraperitoneal ailanthone at 1 or 5 milligrams per kilogram or acyclovir at 5 milligrams per kilogram on days 1, 3 and 5 after infection. The methods section states that six animals were assigned to each group, although the discussion says five mice per group were used in the animal experiment. The 5-milligram-per-kilogram ailanthone treatment significantly reduced clinical disease scores, improved the appearance of the cornea under normal and cobalt-blue illumination, and lowered fluorescein staining scores on days 3 and 5. Hematoxylin and eosin staining at day 6 also indicated reduced corneal inflammation, and viral titers in ocular swabs were significantly lower than in infected mice given vehicle.

Analysis of mouse corneal tissue was consistent with the proposed mechanism. ITGB2 was upregulated in the corneas of infected animals, and ailanthone reduced its fluorescence intensity in a dose-dependent manner. Acyclovir did not significantly alter corneal ITGB2 levels. The investigators interpreted this as evidence that ailanthone differs from a direct viral DNA-replication inhibitor: the data are consistent with modulation of a host dependency factor rather than action solely through a viral enzyme. However, the study did not determine precisely how binding to ITGB2 leads to lower protein abundance. The authors note that transcriptional regulation, changes in messenger-RNA stability, or enhanced protein degradation could all be involved, and dedicated experiments would be required to distinguish among them.

Several limitations constrain how far the findings can be generalized. The cell experiments used established lines, including corneal epithelial and retinal pigment epithelial cells, rather than primary human corneal cells or an intact human immune system. The animal experiment examined acute primary infection in young male mice, whereas recurrent reactivation and the inflammation associated with repeated episodes are important features of human herpes simplex keratitis. Ailanthone was administered by intraperitoneal injection, but no topical ophthalmic formulation, corneal penetration, intraocular distribution, or optimized dosing regimen was evaluated. Long-term ocular toxicity and safety under repeated exposure also remain unknown. The natural compound may additionally affect multiple targets, and compensation among integrins could limit or alter its effects. The evidence therefore supports further preclinical investigation of ailanthone and ITGB2 as a host-directed antiviral strategy, not a clinical recommendation or a claim of human therapeutic benefit.

Subject of Research: Preclinical evaluation of ailanthone as a host-directed inhibitor of HSV-1 replication and herpes simplex keratitis.

Article Title: Natural compound ailanthone alleviates herpes simplex keratitis in mice by inhibiting HSV-1 replication

Article References: Chen, L., Yang, E., Zhang, X., Zhang, L., Wu, L., Chen, S., Jin, W., Qin, Q., Chen, R., Wu, J., & Chen, D. (2026). Natural compound ailanthone alleviates herpes simplex keratitis in mice by inhibiting HSV-1 replication. Frontiers in Pharmacology, 17, Article 1937590. https://doi.org/10.3389/fphar.2026.1937590

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1937590

Keywords: HSV-1, herpes simplex keratitis, ailanthone, ITGB2, host-directed antivirals, viral replication, corneal infection, mouse model, integrin beta 2, drug resistance, Natural, compound

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Palliative care has long been framed as a specialist discipline reserved for hospices and oncology wards, but a growing body of evidence insists it belongs everywhere people approach the end of life, including nursing homes, where a large share of deaths in ageing societies now occur. A new qualitative study from Sweden, published in BMC Nursing, offers an unusually candid look at what happens inside care teams after they receive structured palliative care education, and the central finding is striking: training changes how staff think, but thinking alone does not change care. The researchers, Camilla Ekeblom, Carina Lundh Hagelin and Jane Österlind of Marie Cederschiöld University in Stockholm, found that the value of an educational intervention depends on an intricate alignment between individual emotions, relational dynamics and organisational realities, and that when any one of these dimensions falls out of step, the benefits of education can quietly dissolve.

The study set out to explore how nursing home staff reason about providing palliative care after participating in an interprofessional educational intervention, abbreviated in the literature as IPEI. Rather than measuring outcomes with questionnaires, the team chose a descriptive qualitative design, interviewing eighteen staff members drawn from five Swedish nursing homes. The participants represented the full spectrum of people who actually deliver and manage care: registered nurses, assistant nurses, a physician, first-line managers and designated palliative care champions. This breadth matters, because palliative care in nursing homes is not delivered by any single profession; it emerges, or fails to emerge, from the daily interplay of people with different training levels, responsibilities and emotional exposures to dying residents.

Data were collected through semi-structured individual interviews conducted between March and April 2024, and analysed using inductive qualitative content analysis, a method that allows themes to rise from the material itself rather than being forced into pre-existing theoretical boxes. From this analysis, three main categories emerged, and together they map the terrain on which palliative care is actually practised. The first concerns managing one’s own emotions, thoughts and attitudes. The second addresses the significance of relationships, communication and interactions in care. The third captures how staff navigate norms, assumptions and organisational structures in everyday palliative care. The categories correspond, respectively, to the individual, relational and organisational dimensions of the work, and the authors argue that it is the interplay among all three, not any single factor, that determines whether good palliative care becomes possible.

The individual dimension is perhaps the most human part of the findings. Staff described the ongoing internal work of confronting their own feelings about death, ageing and suffering, and of examining assumptions they carried about what palliative care even means. A recurring tension in the literature, echoed here, is the tendency to equate palliative care narrowly with end-of-life care, the final days and hours, rather than understanding it as an approach that can and should be integrated into everyday care over a longer trajectory. The interviews suggested that the educational intervention gave participants opportunities for personal as well as professional development, creating space to reflect on attitudes that had previously gone unexamined. In this sense, education functioned less like a knowledge transfer and more like a mirror, prompting staff to notice how their own emotional responses shaped their clinical decisions.

The relational dimension proved equally consequential. Palliative care in a nursing home is saturated with communication: conversations with residents about what matters to them, exchanges with distressed relatives, coordination between assistant nurses who know the residents intimately and nurses and physicians who carry clinical responsibility. The participants’ reasoning placed relationships and interactions at the heart of care provision, indicating that no amount of theoretical knowledge substitutes for the ability to build trust, listen and communicate across professional boundaries. This is where the interprofessional design of the intervention appears to have paid off. By bringing different professions into a shared educational space, the programme created a common language and, implicitly, a shared understanding of what the team was trying to achieve together, something that fragmented, profession-specific training often fails to produce.

The third dimension, the organisational, is where the study’s message becomes most uncomfortable for policymakers and care home leadership. Staff described navigating norms and assumptions embedded in their workplaces, along with structural conditions that could either support or obstruct a palliative approach. Staffing levels, routines, leadership priorities and workplace culture all shape what is practically possible on a shift where residents are dying, families are anxious and time is scarce. The authors’ conclusion is explicit on this point: providing palliative care was not solely a matter of enhancing staff knowledge. Knowledge and the conditions for care are shaped through the interplay between staff attitudes, their reasoning about care, relational dynamics and organisational conditions. When these dimensions align and mutually reinforce one another, favourable conditions for palliative care may be supported; when they do not, even well-trained staff may find their intentions frustrated.

Why does this matter on a societal scale? Nursing homes accommodate older people with complex needs and account for a large proportion of deaths, which makes palliative care a central component of care in these settings rather than an occasional emergency. Yet access to palliative care remains unequal, particularly for older people, and staff in long-term care often lack sufficient training. The demographic arithmetic is unforgiving: as populations age, the number of people who will die in nursing homes rises, and the quality of their final months depends heavily on the competence and confidence of the workforce that cares for them. Studies like this one move the conversation beyond the simplistic assumption that a training course fixes the problem, and toward a systems view in which education is necessary but insufficient on its own.

The study also carries a methodological lesson for how we evaluate educational interventions in care settings. Much of the existing research measures knowledge gains or self-reported confidence before and after training. Those metrics are useful, but they cannot reveal how staff actually reason about applying what they have learned in the messy reality of daily care. By using inductive content analysis of interviews, the Swedish team surfaced the texture of that reasoning: the hesitations, the emotional labour, the negotiations with colleagues and managers, the quiet adjustments between ideal practice and what the shift allows. The findings suggest that interprofessional educational initiatives work best when they combine theoretical knowledge with opportunities for reflection and practical application, allowing staff to translate concepts into their own working context rather than leaving translation to chance.

There are limits worth noting. The study involved eighteen participants in five Swedish nursing homes, interviewed at a single point in time after the intervention, and qualitative findings are not designed to be statistically generalised. The researchers themselves submitted the work for ethical review, receiving approval from the Swedish Ethical Review Authority, and obtained written informed consent from all participants, but the transferability of the results to other health systems will depend on how similar those systems’ nursing homes and educational programmes are to the Swedish context. Still, the three-dimensional framework that emerged, individual, relational and organisational, offers a portable lens that other teams can use to examine their own settings, and it aligns with a broader international consensus that palliative care competence must be built at every level of an organisation simultaneously.

The most durable insight from this research may be its refusal to locate the solution in any single place. Staff who completed the intervention perceived it as an opportunity for growth, and their reasoning showed genuine movement in how they understood palliative care as an ongoing approach rather than a final act. But their accounts also made clear that attitudes, relationships and structures must pull in the same direction for that understanding to reach residents’ bedsides. For nursing homes everywhere, the implication is a practical checklist of a different kind: train your staff together, give them room to reflect, examine the norms your workplace quietly enforces, and make sure the organisation’s daily conditions match what the education teaches. Where those elements align, palliative care stops being an aspiration and becomes, simply, the way care is done.

Subject of Research: Nursing home staff's reasoning about providing palliative care after an interprofessional educational intervention

Article Title: “Nursing home staff’s reasoning about providing palliative care following an educational intervention – a qualitative interview study”

Article References: Ekeblom, C., Lundh Hagelin, C., & Österlind, J. (2026). “Nursing home staff’s reasoning about providing palliative care following an educational intervention – a qualitative interview study”. BMC Nursing, 25(1), Article 956. https://doi.org/10.1186/s12912-026-05480-4

Image Credits: AI Generated

DOI: 10.1186/s12912-026-05480-4

Keywords: palliative care, nursing homes, older people, interprofessional education, qualitative research, nursing education, end-of-life care, care staff attitudes, organisational conditions, Sweden, BMC Nursing, healthcare workforce

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