Publications by Year: 2025

This study explores immune responses in mild Omicron-era COVID-19 breakthrough cases, focusing on cytokine dysregulation, antibody dynamics, and Long COVID. Samples from 114 mild COVID-19 patients across multiple waves were analyzed at three timepoints (T1: 2-4 weeks, T2: 3-4 months, T3: 6-8 months post-infection). Persistent IP-10 elevation up to 8 months suggests prolonged low-grade immune activation. Hybrid immunity from Omicron breakthrough infections provided broad cross-variant antibody recognition but showed declining neutralization over time. Among vaccination regimens, mRNA-inclusive combinations were associated with lower Long COVID scores. CoV-229E antibody levels correlated with Long COVID scores. These findings underscore the need for extended monitoring of mild COVID-19 cases and highlight the potential of mRNA vaccines in reducing post-COVID-19 complications. Insights into immune alterations and vaccine effects can inform the development of future vaccination strategies and approaches for managing post-COVID-19 conditions.

Galectins are a family of β-galactosides-binding protein, crucial regulators of host-virus interactions. They achieve this by recognizing specific glycan patterns on viral surfaces or mediating interactions with intracellular viral or host proteins, subsequently influencing the critical phases of the viral life cycle, such as attachment, replication, immune evasion, and reactivation. Furthermore, galectins modulate host immune responses, shaping the progression and outcomes of viral infections. This review comprehensively examines the roles of both endogenous and exogenous galectins in viral infections, noting that only a few galectins, including Galectin-1, -3, -4, -7, -8, and - 9, Have been identified as key players in viral infection. Notably, Galectin-1, -3, and - 9 play diverse functions in both DNA and RNA viral infection. Emerging evidence highlights the potential of Galectin-4 and -8 as intracellular sensors and modulators of viral pathogenesis. Endogenous galectins, produced by host cells, act through both glycan-dependent and glycan-independent mechanisms, influencing viral processes and immune responses. Exogenous galectins, which are secreted by other cells or administered as recombinant proteins, can either enhance or counteract the actions of endogenous galectins. The functions of galectins are virus-specific and context-dependent, serving as either promoters or inhibitors of viral replication and reactivation. Dysregulation of galectin expression is often linked to disease progression, highlighting their potential as diagnostic and prognostic biomarkers, as well as therapeutic targets. The important and varied roles that galectins play in viral infections are highlighted in this review, which also provides fresh insights into host-pathogen interactions and the development of antiviral tactics.

Monkeypox virus (Mpox) has been recognized for causing distinct skin lesions and is primarily transmitted through skin and sexual contact. To date, the transmissibility and pathogenesis of the Mpox virus in distal human lung has never been completely explored. Here the transmission pathways and Mpox tropism on patient-derived air-liquid epithelium (ALE) model fabricated using isolated primary human alveolar epithelial cells (hAECs) were investigated. hAECs were cultured and exposed to the Mpox virus clade IIb isolated from patient. DNA, proteins, and the tropism were elucidated using polymerase chain reaction (PCR), Western blot and high-content fluorescent imaging. Transmission electron microscopy (TEM) was employed to systematically observe the cellular distribution of viral particles. Viral titers were determined by TCID50 assay. Innate immune response and inflammatory mediators were measured using Milliplex® multiplex and ELISA analysis. Pathology at alveolar barrier integrity was determined using transepithelial electrical resistance (TEER) analysis. The study included mock-infected cells as control. Mpox virus significantly infected 42.82% of total hAEC populations. The prominent observed pathology included a significant reduction in TEER values, loss of tight junction protein, presence of tunneling nanotubes (TNTs) and syncytium morphology. Four stages of Mpox biogenesis were clearly observed without significant activation of IL-6, MIP1alpha, TNF-α, and Galectin-9, although IL-1β were subtly promoted. The developed patient-derived ALE is a versatile model for Mpox virus clade IIb infection reflecting respiratory transmission competence of the Mpox. Postinfection lung pathogenesis demonstrated alveolar barrier damage without significant inflammation, raising concerns about possible immune evasion by the virus.

In our study, Prodrug nucleoTide (ProTide) technology was applied to cordycepin to enhance its antiviral activities and metabolic stability. Using cordycepin as starting material, we developed a synthetic method to access a series of stereospecific-phosphoramidate derivatives with various ester groups. We also successfully synthesized halogenated cordycepin derivatives via stannylation. Our 17 ProTide-cordycepin derivatives were pharmacologically evaluated for their antiviral activities. Phosphorus diastereomers 22 S and 22 R showed moderate inhibitory activity against corona and influenza viruses, while these compounds and derivatives (25 S, 27 S, and 27 R) demonstrated promising antiviral efficacy against dengue virus. Pharmacological screening indicated that Sp-isomers generally exhibited slightly greater inhibitory activity than their Rp-isomer counterparts against the dengue virus. The selected ProTides were assessed for their metabolic mechanism and stability via carboxypeptidase and microsomes. The hydrolysis rate of the Rp-isomers was observed to be slightly higher than that of the Sp-isomers, and the addition of a fluorine group also modestly increased this rate and fluorinated 39 S extended its half-life compared to nonfluorinated counterparts. These findings suggested not only structure-activity relationships of cordycepin ProTide but also the comprehensive synthetic route to access cordycepin derivatives for further antiviral development.