Herpes simplex virus type 2 (HSV-2) is the causative pathogen of genital herpes and is closely associated with the occurrence of cervical cancer and human immunodeficiency virus (HIV) infection. The absence of an effective vaccine and the emergence of drug resistance to commonly used nucleoside analogs emphasize the urgent need for alternative antivirals against HSV-2. Recently, ABMA [1-adamantyl (5-bromo-2-methoxybenzyl) amine] has been demonstrated to be an inhibitor of several pathogens exploiting host-vesicle transport, which also participates in the HSV-2 lifecycle. Here, we showed that ABMA inhibited HSV-2-induced cytopathic effects and plaque formation with 50% effective concentrations of 1.66 and 1.08 μM, respectively. We also preliminarily demonstrated in a time of compound addition assay that ABMA exerted a dual antiviral mechanism by impairing virus entry, as well as the late stages of the HSV-2 lifecycle. Furthermore, in vivo studies showed that ABMA protected BALB/c mice from intravaginal HSV-2 challenge with an improved survival rate of 50% at 5 mg/kg (8.33% for the untreated virus infected control). Consequently, our study has identified ABMA as an effective inhibitor of HSV-2, both in vitro and in vivo, for the first time and presents an alternative to nucleoside analogs for HSV-2 infection treatment.

Glycyrrhiza polysaccharide extract 1 (GPS-1) is a bioactive component isolated from Glycyrrhiza uralensis, also known as Chinese licorice. It appears to be pharmacologically active as an antibacterial, antiviral, and anti-tumor agent. GPS-1 has also been shown to buffer liver health and regulate the immune system. Moreover, GPS-1 is low cost and easy to extract. More study was needed to elucidate the biochemical pathways underlying the immunomodulatory and antioxidant benefits observed in Glycyrrhiza polysaccharide extract 1 (GPS-1). in vitro experiments on chicken lymphocytes and dendritic cells (DCs) show that GPS-1 significantly promotes the proliferation of immune cells and is linked to lymphocytes' secretion of IL-12, IFN-γ, and TNF-α by. DC secretion of NO, IL-2, IL-1β, IFN-γ, TNF-α, and IL-12p70 was also increased significantly. Additionally, GPS-1 also displayed a significant antioxidant effect in vitro, able to scavenge DPPH, hydrogen peroxide, ABTS, and other free radicals like superoxide anions. Separately, GPS-1 was tested in vivo in combination with the Newcastle disease virus (NDV) – attenuated vaccine. 120 Lohmann Brown chickens were vaccinated, while another 30 became the unvaccinated blank control (BC) group. For three consecutive days 1 mL of GPS-1 was administered at doses of 19.53 μg/mL, 9.77 μg/mL, or 4.88 μg/mL to the ND-vaccinated birds, except for the vaccine control (VC), where n = 30 per group. In vivo results show that GPS-1 combined with Newcastle disease (ND) vaccine had the best efficacy at significantly increasing chickens' body weight and ND serum antibody titer, enhancing their secretion of IL-2 and IFN- γ, and promoting the development of immune organs. The results also indicate that GPS-1 was able increase the proliferation of in vitro immune cells and elevate their cytokine secretion, which enhances the body's immune response. GPS-1 also clearly has the potential to be used as an immune adjuvant alongside ND vaccination.

Intracellular pathogenic microorganisms and toxins exploit host cell mechanisms to enter, exert their deleterious effects as well as hijack host nutrition for their development. A potential approach to treat multiple pathogen infections and that should not induce drug resistance is the use of small molecules that target host components. We identified the compound 1-adamantyl (5-bromo-2-methoxybenzyl) amine (ABMA) from a cell-based high throughput screening for its capacity to protect human cells and mice against ricin toxin without toxicity. This compound efficiently protects cells against various toxins and pathogens including viruses, intracellular bacteria and parasite. ABMA provokes Rab7-positive late endosomal compartment accumulation in mammalian cells without affecting other organelles (early endosomes, lysosomes, the Golgi apparatus, the endoplasmic reticulum or the nucleus). As the mechanism of action of ABMA is restricted to host-endosomal compartments, it reduces cell infection by pathogens that depend on this pathway to invade cells. ABMA may represent a novel class of broad-spectrum compounds with therapeutic potential against diverse severe infectious diseases.

Natural killer (NK) cells have shown great therapeutic potential against a wide range of cancers due to their pan-specific target recognition. Numerous reports indicate that NK cell immunotherapy is an effective therapeutic approach for treating hematological malignancies, but shows limited effects against solid tumors. In this study, several models of ovarian cancer (OC) were used to test the anti-cancer effects of NK cells derived from human peripheral blood mononuclear cells and expanded using a feeder cell-free expansion system (eNKs). The results show that eNKs exhibit potent inhibitory activity on tumor growth in different ovarian cancer xenograft mice (i.e., solid tumors, abdominal metastatic tumors, and ascites), importantly, in a dose-dependent manner. Moreover, adoptive transfer of eNKs resulted in significant reduction in ascites formation in OC peritoneal tumor models, and especially in reducing intraperitoneal ascites. We found that eNKs could migrate to the tumor site, retain their activity, and proliferate to maintain high cell counts in cutaneous xenograft mice. In addition, when increased the infusion with a high dose of 12 × 10⁷ cells/mouse, Graft-versus-host disease could be induced by eNK. These data show that eNK cell immunotherapy could be a promising treatment strategy for ovarian cancers, including solid tumors and ascites.

The endo‐lysosome system is involved in endocytosis, protein sorting, and degradation as well as autophagy. Numerous toxins and pathogens exploit this system to enter host cells and exert their deleterious effects. Modulation of host endo‐lysosome pathway may restrict multiple toxins intoxication as well as pathogen infection. ABMA, selected from a high‐throughput screening against the cytotoxicity of ricin toxin, exhibits a broad‐spectrum antitoxin and antipathogen activity. Here, we show that ABMA selectively retains endocytosed protein and toxin to late endosomes and thus delaying their intracellular trafficking. It also impairs the autophagic flux by excessive fusion of late endosomes and autophagosomes. Its exclusive action on late endosomes and corresponding consequences on the endo‐lysosomal pathway and autophagic flux are distinct from known inhibitors such as bafilomycin A1, EGA, or chloroquine. Hence, besides being a broad‐spectrum inhibitor of endocytosed toxins and pathogens, ABMA may serve as a molecular tool to dissect endo‐lysosome system‐related cellular physiology and mechanisms of pathogenesis.