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Tobacco mosaic virus (TMV) is a major agricultural threat. Here, a cationic star polymer (SPc) was designed to construct an efficient nanodelivery system for moroxydine hydrochloride (ABOB). ABOB could self-assemble with SPc via a hydrogen bond and van der Waals force, and this complexation reduced the particle size of ABOB from 2406 to 45 nm. With the aid of SPc, the contact angle of ABOB decreased from 100.8 to 79.0°, and its retention increased from 6.3 to 13.8 mg/cm 2 . Furthermore, the complexation with SPc could attenuate the degradation of ABOB in plants, and the bioactivity of SPc-loaded ABOB significantly improved with a reduction in relative viral expression from 0.57 to 0.17. The RNA-seq analysis revealed that the ABOB/SPc complex could up-regulate the expression of growth- and photosynthesis-related genes in tobacco seedlings, and the chlorophyll content increased by 2.5 times. The current study introduced an efficient nanodelivery system to improve the bioactivity of traditional antiviral agents.

Our previous studies have verified that moroxydine hydrochloride (Mor) could inhibit replication of grass carp reovirus (GCRV) and suppress apoptosis of Ctenopharyngodon idella kidney cells, but be lack of information whether exists on antiviral activity in vivo. The paper was undertaken to explore the antiviral response of Mor against GCRV in grass carp and investigate the safety of drug for aquatic organisms. The results showed that injection treatment of Mor could more effectively inhibit GCRV replication than immersion administration. All the RNA systheses of vp3 and vp6 on day 7 in head kidney, gill, hepatopancreas and dorsal muscle in the Mor injection group were lesser than 0.07‐fold than that of in control group. And the GCRV‐inducing grass carp mortality was effectively controlled within 7 days post Mor injection therapy. Additionally, the reduction of superoxide dismutase activity, total antioxidant capacity and catalase activity in serum was effectively controlled by Mor. Moreover, drug safety assessment results showed that 500 mg/L of Mor was safe to C. idella, Bacillus subtilis, Chlorella vulgaris and Tetrahymena thermophila, which was far higher than the therapeutic concentration. The present study proved Mor as harmless formulations or products had potential value in the control of GCRV in aquaculture, with the advantage of super in vivo antiviral activity and environmental safety. [ABSTRACT FROM AUTHOR]

Complexes of moroxydine hydrochloride (ABOB) with cucurbit[ n]urils (n = 7 or 8) were investigated using H NMR spectroscopy, Quadrupole-Time of Flight mass spectrometry (Q-TOF), UV absorbance spectrophotometry, isothermal titration calorimetry (ITC), and X-ray crystallography. Experimental results revealed that the morpholino group of ABOB resides within the cavity of Q[7] and Q[8] respectively in both aqueous solution and solid state. In aqueous solution, 1:1 inclusion complexes of ABOB and Q[7,8] are formed with moderate binding constants. In the solid state, the cavity of Q[8] encapsulates two ABOB morpholine groups to generate a novel 2ABOB@Q[8] inclusion complex. Graphical abstract: [ABSTRACT FROM AUTHOR]

Moroxydine hydrochloride (Mor) is known to have multi-antiviral activities against DNA and RNA viruses but very little information exists on its pharmacology. The paper was undertaken to explore the antiviral response and antiapoptotic mechanism of Mor against grass carp reovirus (GCRV) in Ctenopharyngodon idella kidney (CIK) cells. The results showed that exposing GCRV-infected cell to 6.3 μg mL −1 of Mor for 96 h avoid ca. 50% apoptosis. Meanwhile, Mor had lower cytotoxicity than ribavirin (Rib) as the value of safe concentration was threefold higher than effective concentration and the compound could ensure sufficient into and out of cells within 4 h when tested at the maximal safe concentration. Mor blocked the GCRV-induced cytopathic effects and eliminated nucleocapsids in CIK cells to keep the normal morphological structure. Moreover, the expressions of viral protein genes were significantly inhibited especially the guanylyl transferase and RNA-dependent RNA polymerase related expression. Furthermore, GCRV caused Bcl-2 down-regulation and Bax mitochondrial translocation was prevented by treatment of CIK cells with Mor. The downstream effector, caspase activity was also significantly inhibited in Mor treated cells. The potential mechanism might be that mitochondrial apoptotic signals were not activated by the intervention of Mor for targeting viral gene expression. Taken together, Mor showed high anti-GCRV activity and had been proved as a secure and promising agent in viral controlling in aquaculture industry. [ABSTRACT FROM AUTHOR]

[Objective] To eliminate virus while minimizing the harmful side effect to the yam plants, efficiency of antiviral drugs to eliminate the Yam mild mosaic virus (YMMV) in yams was evaluated so as to develop a new method for generating virus-free yam seedlings. [ Method ] Broad-spectrum antiviral drugs ribavirin, moroxydine hydrochloride and acyclovir at varied concentrations (10, 20, 30, 40, 50 mg/L) were implemented into the culture media to treat the stems of YMMV-infected yam (D. alata) Yuebei No.3 (YB3), respectively. The resulting yam plantlets were examined by YMMV-specific RT-PCR. [Result'Ribavirin at concentration of 40 mg/L or higher significantly inhibited the growth of yam plantlets, whereas moroxydine hydrochloride and acyclovir hardly exhibited any inhibition. No virus was detected when treated with ribavirin at 40 mg/L or higher concentration, and moroxydine hydrochloride and acyclovir at 30 mg/L or higher concentration for three months. [Conclusion'Treatment of yam stems with moroxydine hydrochloride and acyclovir at concentration of 30 -50 mg/L for three months could eliminate YMMV from the regenerated yam plantlets and these two drugs are better than ribavirin at the same concentration. [ABSTRACT FROM AUTHOR]

Infectious diseases of viral origin cause major aquatic production losses in different parts of the world. There are lots of limited therapeutic effects for large amounts of antiviral drugs because of several impenetrable barriers (cell, skin, and gastrointestinal tract). In this study, we selected moroxydine hydrochloride (Mor) for the treatment of infectious spleen and kidney necrosis virus (ISKNV) and choose single-walled carbon nanotubes (SWCNTs) as drug carrier by immersion bath on mandarin fish infected with ISKNV. The results showed that increasing Mor intake was observed by SWCNTs carrier and therapeutic dosage to kill ISKNV is significantly reduced. After 4 h treatment, the concentration of Mor was 103.48 μg/g in 40 mg/L Mor group, and 182.35 μg/g in 40 mg/L Mor-SWCNTs groups. Comparing with the same dosage in Mor group, the detention time of Mor was extended more than 48 h in Mor-SWCNTs group. After 11 d treatment, cumulative mortality was 11.51% and infection rate was 3.81% in 40 mg/L Mor-SWCNTs group. In the same dosage of Mor group, cumulative mortality was 43.34% and infection rate was 22.67%. Moreover, enzyme activities, complement (C3) content and immune-related genes expression were significantly increased in Mor and Mor-SWCNTs groups than control group, herein all these mentioned activities reached the highest level at 3 days post-treatment. Our results indicated that drug delivery with functionalized SWCNTs can improve the antiviral effect on mandarin fish and has a potential application value to control fish viral diseases in aquaculture. • Our study indicated that Mor delivery with functionalized SWCNTs can improve the antiviral effect on mandarin fish. • Comparing with the same dosage in Mor group, the detention time of Mor was extended more than 48 h in Mor-SWCNTs group. • Our study showed that Mor-SWCNTs can be a plausible candidate for preventing and controlling ISKNV in farmed mandarin fish. [ABSTRACT FROM AUTHOR]

Moroxydine hydrochloride (Mor) and ribavirin (Rib) are known for their multi-antiviral activities against DNA and RNA viruses but little information is available about the pharmacological impact in aquaculture. The present study was undertaken to investigate the response of host cells to antiviral compounds during the anti-GCRV treatment. The scanning electron microscope results showed that Ctenopharyngodon idella kidney (CIK) cells have a higher death rate at 72h post virus infection. At the concentration of 40μgmL -1 , Mor and Rib had a significant protective effect on virus-infected cells. Moreover, the gene expressions of vp5, vp6 and NS66 were significantly inhibited by treatment with Mor or Rib, especially gene expression of the vp5. For the immunoregulatory action, no distinct induction of the expression of immune genes was observed after the addition of Mor and Rib to the virus-free cells. However, the compounds significantly decreased the virus-induced gene overexpression of Myd88, Mx1, IL-1β, IL-8, I-IFN and TNFα in CIK cells. Moreover, Mor and Rib significantly inhibited the immune genes upregulation which was induced by GCRV in kidney, liver, muscle and gill of grass carp, despite greater partial gene expressions were detected than the virus-free control group. Besides, Mor and Rib blocked cell cycle changes, cytopathic effects, cellular death and virus proliferation in CIK cells thereby maintaining normal morphological structure. Overall, Mor and Rib as antiviral compounds are effective for the control of GCRV replication and the indirectly regulation of cellular immune response., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Moroxydine hydrochloride (Mor) and ribavirin (Rib) have been reported to exhibit multi-antiviral activities against DNA and RNA viruses, but their antiviral activities and pharmacologies have seldom been studied in aquaculture. This paper has selected 3 aquatic viruses including a double-stranded RNA virus (grass carp reovirus, GCRV), a single-stranded RNA virus (spring viraemia of carp virus, SVCV) and a DNA virus (giant salamander iridovirus, GSIV) for antiviral testing. The results showed that Mor and Rib can effectively control the infection of GCRV and GSIV in respective host cells. Further study was undertaken to explore the antivirus efficiencies and pharmacological mechanisms of Mor and Rib on GCRV and GSIV in vitro. Briefly, compounds showed over 50% protective effects at 15.9 µg ml-1 except for the group of GSIV-infected epithelioma papulosum cyprinid (EPC) cells treated with Mor. Moreover, Mor and Rib blocked the virus-induced cytopathic effects and apoptosis in host cells to keep the normal cellular structure. The expression of VP1 (GCRV) and major capsid protein (MCP; GSIV) gene was also significantly inhibited in the virus-infected cells when treated with Mor and Rib. Cytotoxicity assay verified the 2 compounds had no toxic effects on grass carp ovary (GCO) cells and EPC cells at ≤96 µg ml-1. In conclusion, these results indicated that exposing GCRV-infected GCO cells and GSIV-infected EPC cells to Mor and Rib could elicit significant antiviral responses, and the 2 compounds have been shown to be promising agents for viral control in the aquaculture industry.