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

A retrospective study of 1,307 patients undergoing elective percutaneous vertebroplasty for osteoporotic vertebral compression fractures found that 136, or 10.4%, had a puncture-site wound event within two weeks of surgery. The composite outcome included erythema or swelling, bleeding or exudate, subcutaneous hematoma, and infection. After adjustment for patient and procedural factors, suture closure was associated with more than twice the risk of the composite outcome, while diabetes, mildly elevated international normalized ratio, and multilevel treatment were also associated with higher risk.

The findings come from consecutive patients treated at Ningde Municipal Hospital in China between January 2022 and June 2026. Patients were excluded if they underwent surgery for a new fracture, had uncontrolled coagulation disorders, received concomitant open spinal surgery, required an intraoperative incision at the puncture site, had malignant tumors or abnormal immune status, or lacked key clinical or follow-up information. The analysis therefore describes elective vertebroplasty performed within one hospital system, rather than all fracture patients or all puncture wounds treated after other forms of spine surgery.

Researchers extracted information from electronic medical records, operative and anesthesia records, laboratory reports, dressing-change notes, wound-clinic assessments, and documented telephone follow-up. All puncture sites were covered with waterproof dressings and assessed within two weeks through inpatient observation, clinical review, or telephone follow-up. A wound event was counted only when explicitly documented in the records. Erythema, swelling, bleeding, exudate, hematoma, and infection were combined into one patient-level outcome, counted once even if a patient experienced several types of event, while individual components were also summarized separately.

Closure was not assigned through a randomized comparison. The operating physician selected nonsuture or suture closure according to intraoperative bleeding, exudation, skin condition, wound tension, and routine practice. Sutured wounds were typically closed with one 3-0 Vicryl Rapide stitch. Among the 1,307 patients, 774 received nonsuture closure and 533 received sutures. An early event was recorded in 53 nonsuture cases, or 6.8%, and in 83 sutured cases, or 15.6%. The crude risk ratio for any event was 2.27, with a 95% confidence interval of 1.64 to 3.15 and a P value below 0.001.

After the researchers adjusted for closure method, diabetes, INR above 1.2, age, sex, body mass index, and multilevel treatment, the association with suturing remained. The adjusted risk ratio was 2.24, with a 95% confidence interval of 1.59 to 3.16 and P below 0.001. Diabetes was associated with an adjusted risk ratio of 1.57, with a 95% confidence interval of 1.11 to 2.21 and P equal to 0.010. An INR above 1.2, defined using the hospital laboratory’s upper reference limit, was associated with an adjusted risk ratio of 1.66, with a 95% confidence interval of 1.08 to 2.57 and P equal to 0.022. Multilevel treatment had an adjusted risk ratio of 1.73, with a 95% confidence interval of 1.03 to 2.89 and P equal to 0.038.

The component findings were concentrated in relatively common superficial manifestations rather than infection. Erythema or swelling occurred in 4.1% of patients with nonsuture closure and 10.9% of those with sutures, producing a crude risk ratio of 2.63, with a 95% confidence interval of 1.73 to 3.99. Bleeding or exudate occurred in 2.7% and 5.8% of the respective groups, with a crude risk ratio of 2.14 and a 95% confidence interval of 1.25 to 3.69. Subcutaneous hematoma was uncommon, affecting two nonsuture cases and three sutured cases, and its wide confidence interval included no difference. Infection was documented in one nonsuture case and no sutured cases, too few events to model infection separately.

Age, sex, and body mass index were not independently associated with the composite outcome in the primary adjusted model. Each additional decade of age had an adjusted risk ratio of 1.15, with a 95% confidence interval of 0.94 to 1.41 and P equal to 0.186. Female sex had an adjusted risk ratio of 0.96, with a 95% confidence interval of 0.66 to 1.39 and P equal to 0.829, while each 1 kg/m² increase in body mass index had an adjusted risk ratio of 1.07, with a 95% confidence interval of 0.99 to 1.17 and P equal to 0.091. These estimates mean that the study did not find clear independent associations for those demographic and anthropometric measures, not that they have no relationship to wound events in every clinical setting.

The suture result is particularly notable because the design cannot establish that suturing caused the additional events. The authors excluded several conditions that could make closure decisions unusual, including uncontrolled coagulation disorders, concomitant open surgery, and wounds requiring an intraoperative incision. Even so, surgeons may have selected sutures for locally difficult wounds, bleeding, exudation, poor skin condition, or excessive tension. Those unrecorded features could confound the comparison, while the fact that sutured patients may have had more wound checks or suture-removal visits could also increase the likelihood that mild redness or exudate was noticed and recorded. The finding should therefore be interpreted as an adjusted observational association rather than proof that sutures themselves produce wound inflammation or other complications.

Several other constraints limit what the study can establish. Follow-up was retrospective and varied among inpatient observation, wound-clinic examination, and telephone reporting, so assessment intensity and recording thresholds were not standardized. Very mild redness or transient bleeding may have been missed, and the records did not consistently capture event duration, patient discomfort, additional care, revisits, or hospitalization. The composite endpoint improved capture of local findings but combined conditions with different causes and severities. Only one infection occurred within two weeks, preventing meaningful analysis of surgical-site infection or later infections. The single-center design and the selected elective population also limit generalizability to open spine surgery, malignant disease, immunosuppression, or puncture sites requiring remedial closure.

Overall, the study identifies four factors associated with the short-term local wound status after elective vertebroplasty: suture closure, diabetes, elevated INR, and multilevel treatment. Its practical signal is that early observation may be especially relevant for patients with these characteristics, although the findings do not establish a clinical rule or a preferred closure technique. Because closure was clinician-selected, follow-up was not standardized, and the endpoint combined mild events with rare infection, the results point to priorities for further prospective research rather than definitive guidance. Within those limits, the observed 15.6% event rate after suturing compared with 6.8% after nonsuture closure provides the clearest signal in the cohort, while the observational design makes the mechanism unresolved.

Subject of Research: Factors associated with early puncture-site wound events after percutaneous vertebroplasty for osteoporotic vertebral compression fractures

Article Title: Factors associated with early puncture-site wound events after percutaneous vertebroplasty for osteoporotic vertebral compression fractures: a retrospective cohort study

Article References: He, X., Huang, C., Zheng, B., Wu, X., Huang, C., Lu, S., Huang, Y., Chen, J., Huang, J., & Li, B. (2026). Factors associated with early puncture-site wound events after percutaneous vertebroplasty for osteoporotic vertebral compression fractures: a retrospective cohort study. Frontiers in Medicine, 13, Article 1988843. https://doi.org/10.3389/fmed.2026.1988843

Image Credits: AI Generated

DOI: 10.3389/fmed.2026.1988843

Keywords: Percutaneous vertebroplasty, Osteoporotic fractures, Puncture-site wounds, Suture closure, Diabetes, Coagulation, Multilevel treatment, Retrospective cohort, Postoperative care, Factors, associated, early