Assessment of antiviral activity and mechanism of rhein on newcastle disease virus (La Sota strain IV) in vitro.

Current research is focused on the development of drug candidates from natural products. Rhein a Traditional Chinese Medicine (TCM) from Polygonaceae (rhubarb) has exhibited antioxidant, anti-inflammatory and anticancer activities, however no work has reported its antiviral potential, thus this study was performed to investigate the antiviral activities of rhein on new castle disease virus (NDV) in vitro.NDV infection of chicken embryo fibroblasts (CEFs) was prepared using 10-day-old specific pathogen free chicken embryos. Cytotoxicity and anti-viral activities of rhein were assessed using the MTT method. The interaction between NDV and cell membrane proteins were also detected using virus overlay protein binding assay (VOPBA). In addition NDV genes expressions in CEFs were measured using real-time fluorescent quantitative (RTFQ) PCR.The results showed that rhein effectively inhibit NDV activities maximal safe concentration of 0.125 mg/ml. This finding indicated that, rhein could be used as future antiviral drug against NDV.[Formula: see text].

In silico, in ovo and in vitro antiviral efficacy of phosphorylated derivatives of abacavir: an experimental approach.

Outstanding increase of oral absorption, bioavailability, and antiviral efficacy of phosphorylated nucleosides and basic antiviral influence of abacavir is the central idea for the development of new series of phosphorylated abacavir (ABC) derivatives. The designed compounds were primarily screened for antiviral nature against HN protein of NDV and VP7 protein of BTV using the molecular environment approach. Out of all the designed compounds, the compounds which are having higher binding energies against these two viral strains were prompted for the synthesis of the target compounds (5A-K). Among the synthesized title compounds (5A-K), the compounds which have exhibited higher dock scores akin to the rest of the compounds were then selected and screened for the antiviral activity against NDV and BTV infected embryonated eggs and BHK 21 cell lines through the in ovo and in vitro approaches. The results revealed that all the designed compounds have formed higher binding energies against both the targets. Among all, the compounds which are selected based on their dock scores such as 5A, 5F, 5G, 5H, 5I, and 5K against NDV and 5J, 5E, 5I, 5C, 5A, and 5K against BTV have shown significant antiviral activity against HN protein of NDV, VP7 protein of Bluetongue virus in both NDV- and BTV-treated embryonated eggs and BHK 21 cell lines. Hence, it is concluded that, the best lead compounds will stand as the potential antiviral agents and prompted them as virtuous therapeutics against NDV and BTV in future.

Anti-NDV activity of 9-oxo10,11-dehydroageraphorone extracted from Eupatorium adenophorum Spreng in vitro.

The purpose of this study was to investigate the anti-Newcastle disease virus (NDV) activities of 9-oxo-10,11-dehydroageraphorone (euptox A) from Eupatorium adenophorum Spreng (E. adenophorum) in vitro. NDV infection of chicken embryo fibroblasts (CEFs) was performed. Cytotoxicities and antiviral activities of euptox A was assessed by the MTT method. The interaction of NDV with cell membrane protein was detected by virus overlay protein binding assay (VOPBA). The expression levels of NDV genes in CEFs was tested by RTFQ PCR. The results showed that the maximal safe concentrations of euptox A to CEFs was 10 µg/mL. Euptox A could directly neutralise NDV, inhibit the infectivity of NDV to CEFs and block intracellular NDV treat NDV infection. And euptox A brings competitiveness inhibition for NDV binding to its receptors and then prevent NDV infection. These results indicated that euptox A possessed anti-NDV activity has potential use as components of a natural antiviral drug.

A Raf kinase inhibitor demonstrates antiviral activities both in vitro and in vivo against different genotypes of virulent Newcastle disease virus.

Newcastle disease (ND) is still one of the major plagues of birds worldwide. Combat actions are limited to vaccines, highlighting the urgent need for new and amply available antiviral drugs. Previous results have shown that Newcastle disease virus (NDV) downregulates the intracellular Raf kinase inhibitor protein (RKIP) expression for efficient replication, suggesting that this molecular may be a suitable target for antiviral intervention. In the present work, we investigated whether or not the Raf kinase inhibitor V (RKIV), which functions in the same way as RKIP by targeting the intracellular Raf kinase, is able to suppress the propagation of enzootic virulent NDV in vitro and in vivo. In vitro antiviral activity of RKIV was assessed by cell-based assay, and in vivo activity was determined in the chicken model. Our results clearly showed that RKIV treatment protected the cells from NDV-induced CPE with the effective concentrations on nM level, and inhibited virus replication in the lungs of infected chickens in a dose-dependent manner and protected chickens from the lethal infection by NDV. Thus, we conclude that the Raf kinase inhibitor compound RKIV, by inhibiting the host cellular target Raf kinase, might be very promising as a new class of antivirals against the enzootic virulent NDV infection.

Design, Synthesis and Biological Evaluation of Novel Phosphorylated Abacavir Derivatives as Antiviral Agents Against Newcastle Disease Virus Infection in Chicken.

Newcastle disease virus is the most devastating virus in poultry industry. It can eradicate the entire poultry flocks once infected. This study is aimed to investigate the antiviral efficacy of novel phosphorylated analogues of the drug abacavir (ABC) against Newcastle disease virus (NDV). About 16 analogues of ABC were designed and docking was performed against fusion protein of NDV. Three compounds were identified and selected for synthesis and biological evaluation based on binding affinity and docking scores. The compounds were synthesized and characterized by IR, (1)H, (13)C, (31)P and CHN analysis and mass spectra. These compounds were tested for antiviral efficacy against NDV-infected DF-1 cells. Compound ABC-1 had shown potent antiviral activity as evidenced by significant reduction in plaque units and cytopathic effect. Therefore, ABC-1 was selected to test for NDV-infected chicken survival rate. Effective dose50 concentrations were determined for ABC-1. Antioxidant enzyme levels in brain, liver and lung tissues were estimated. Superoxide dismutase and catalase were significantly raised and lipid peroxidation and HA titer levels were decreased upon treatment with 2 mg/kg body weight ABC-1. Histopathological modifications were also restored in the ABC-1-treated group. These findings demonstrated ABC-1 as a potential antiviral agent against NDV in chicken.

Immunomodulatory effects of Taishan Pinus massoniana pollen polysaccharide and propolis on immunosuppressed chickens.

Co-infection of reticuloendotheliosis virus (REV) and avian leukosis virus subgroup J (ALV-J), which can cause suppressed immunity and vaccination failure, frequently occurs in chicken flocks in China. Taishan Pinus massoniana pollen polysaccharide (TPPPS) and propolis (PP) have been proven to possess immune modulatory effects and improve the immune effects of vaccines. This study aimed to investigate the immune modulatory ability of TPPPS and PP on chickens co-infected with immunosuppressive viruses. Prior to the study, chickens were artificially established as REV and ALV-J co-infection models. Four randomly assigned groups of these immunosuppressed chickens were successively administered with TPPPS, PP, mixture of TPPPS and PP (TPPPS-PP), or phosphate-buffered saline (PBS) for three days. At nine days old, the four immunosuppressed groups, as well as one normal group, were inoculated with the attenuated Newcastle disease (ND) vaccine. During the monitoring period, the indices of immune organ weight, lymphocyte transformation rates, CD4(+) and CD8(+) T-lymphocyte counts in peripheral blood, IL-2 and IFN-γ secretions, serum antibody titers of ND vaccine, and viral loads in spleens were determined. The results showed that chickens administered with TPPPS, PP, or TPPPS-PP could significantly enhance the levels of the above immune parameters compared to chickens in the PBS group. We observed the strongest immunity in the TPPPS-PP group, which indicates that the combination of TPPPS and PP versus TPPPS or PP alone, could generate better effects on improving the immune system effectiveness of immunosuppressed chickens.

A cholesterol tag at the N terminus of the relatively broad-spectrum fusion inhibitory peptide targets an earlier stage of fusion glycoprotein activation and increases the peptide's antiviral potency in vivo.

In previous work, we designed peptides that showed potent inhibition of Newcastle disease virus (NDV) and infectious bronchitis virus (IBV) infections in chicken embryos. In this study, we demonstrate that peptides modified with cholesterol or 3 U of polyethylene glycol (PEG3) conjugated to the peptides' N termini showed even more promising antiviral activities when tested in animal models. Both cholesterol- and cholesterol-PEG3-tagged peptides were able to protect chicken embryos from infection with different serotypes of NDV and IBV when administered 12 h prior to virus inoculation. In comparison, the untagged peptides required intervention closer to the time of viral inoculation to achieve a similar level of protection. Intramuscular injection of cholesterol-tagged peptide at 1.6 mg/kg 1 day before virus infection and then three times at 3-day intervals after viral inoculation protected 70% of the chickens from NDV infection. We further demonstrate that the cholesterol-tagged peptide has an in vivo half-life greater than that of untagged peptides. It also has the potential to cross the blood-brain barrier to enter the avian central nervous system (CNS). Finally, we show that the cholesterol-tagged peptide could play a role before the viral fusion peptide's insertion into the host cell and thereby target an earlier stage of fusion glycoprotein activation. Our findings are of importance for the further development of antivirals with broad-spectrum protective effects.

[Interferonogenic and antiviral activity of the tobacco mosaic virus, tilorone and sodium nucleinate]. / Interferonogennaia i protivovirusnaia aktivnost' virusa tabachnoi mozaiki, tilorona i nukleinata natriia

Production of endogenic interferon in animals in responce to administration of tobaco mozaic virus, tilorone and sodium nucleinate was shown. Dependence of interferon production on the type of the inductor and the route of its administration was studied. Absolute innocuiuty of the tobaco mozaic virus for monkeys (macaco-resus) and mice, as well as the absence of any side effects in humans treated with it perorally was shown. The tobaco mozaic virus, tilorone and sodium nucleinate used perorally in treatment of experimental infections of mice caused by the viruses of East and West encephalomyelitis, influenza and tick encephalitis had a pronounced protective effect.