Antiviral Activity Exerted by Natural Products against Human Viruses.

Viral infections are responsible for several chronic and acute diseases in both humans and animals. Despite the incredible progress in human medicine, several viral diseases, such as acquired immunodeficiency syndrome, respiratory syndromes, and hepatitis, are still associated with high morbidity and mortality rates in humans. Natural products from plants or other organisms are a rich source of structurally novel chemical compounds including antivirals. Indeed, in traditional medicine, many pathological conditions have been treated using plant-derived medicines. Thus, the identification of novel alternative antiviral agents is of critical importance. In this review, we summarize novel phytochemicals with antiviral activity against human viruses and their potential application in treating or preventing viral disease.

OsHV-1 infection leads to mollusc tissue lesion and iron redistribution, revealing a strategy of iron limitation against pathogen.

The mass mortality of molluscs caused by OsHV-1 infection has frequently occurred worldwide in recent years. Meanwhile the interaction between OsHV-1 and its host is largely unknown. Innate immunity mainly makes up the mollusc defense system, due to the lack of adaptive immunity in invertebrates. The iron limitation strategy is an indispensable facet of innate immunity across vertebrate and invertebrate species. In this study, an iron limitation strategy was interestingly found to contribute to mollusc innate immune responses against OsHV-1 infection. Firstly, ark clams, Scapharca broughtonii, were experimentally infected with OsHV-1, and serious hyperaemia in hepatopancreases and the erosion of gills were observed post OsHV-1 infection according to a histology assay. Meanwhile, based on quantification and Prussian blue staining, the process of iron efflux from ark clams was described post OsHV-1 infection. Secondly, ferritin, as an important iron storage protein, was characterized in ark clams and showed significant iron binding activity. According to the results of an immunohistochemistry assay, ferritin was supposed to be responsible for the iron translocation in ark clams post OsHV-1 infection. Its expression level was significantly fluctuant in response to OsHV-1 infection. Finally, oxidative stress was assessed by the analyses of H2O2 content, total antioxidant capacity and MDA level post OsHV-1 infection. Supplementary iron was found to promote ROS generation and death of hemocytes in vivo. These results highlighted that microenvironment changes in the essential nutrient iron should be an important aspect of the pathogenesis of OsHV-1 disease.

Identification and characterization of a ferritin gene involved in the immune defense response of scallop Chlamys farreri.

Scallop Chlamys farreri is an important aquaculture species in northern China. However, its mass mortality caused by several pathogens can result in great economic loss and negative impacts to the sustainable development of the scallop industry. Thus, improving the overall understanding of immune response mechanisms involved in host-pathogen interactions is necessary. Ferritins are conserved molecules in organisms that are involved in diverse biological processes, such as mediating host-pathogen responses. In this study, we report a novel ferritin gene from C. farreri (denoted as CfFER). The full length of CfFER is 848 bp and contains a 5'-UTR of 113 bp, a 3'-UTR of 219 bp, and a complete open reading frame (ORF) of 516 bp. The ORF encodes a polypeptide of 171 amino acid residues with a molecular weight of approximately 19.95 kDa and an isoelectric point of 5.07. The CfFER protein exhibited typical ferritin structures, namely, a ferroxidase diiron center, a ferrihydrite nucleation center, and an iron-binding response signature. Phylogenetic analysis revealed that CfFER was closely related to other mollusk ferritin proteins. Expression of CfFER in different tissues was analyzed by quantitative real-time PCR, and results showed that CfFER was ubiquitously expressed in all examined tissues. The highest and lowest expression levels of CfFER were measured in the muscle and hemocyte, respectively. The relative mRNA expression of CfFER in response to bacterial (Vibrio anguillarum) and viral (acute viral necrobiotic virus) challenges sharply increased by ca. 5-fold about12 h post-infection (hpi) and then normalized at 48 hpi. Western blot analysis with polyclonal antibodies generated from the recombinant product of CfFER also demonstrated the presence of ferritin protein in hemocytes. These findings strongly suggest that CfFER is involved in the immune response of C. farreri and protection against pathogen challenge.

Toward the discovery of dual HCMV-VZV inhibitors: Synthesis, structure activity relationship analysis, and cytotoxicity studies of long chained 2-uracil-3-yl-N-(4-phenoxyphenyl)acetamides.

The need for novel therapeutic options to fight herpesvirus infections still persists. Herein we report the design, synthesis and antiviral evaluation of a new family of non-nucleoside antivirals, derived from 1-[ω-(4-bromophenoxy)alkyl]uracil derivatives--previously reported inhibitors of human cytomegalovirus (HCMV). Introduction of the N-(4-phenoxyphenyl)acetamide side chain at N(3) increased their potency and widened activity spectrum. The most active compounds in the series exhibit submicromolar activity against different viral strains of HCMV and varicella zoster virus (VZV) replication in HEL cell cultures. Inactivity against other DNA and RNA viruses, including herpes simplex virus 1/2, points to a novel mechanism of antiviral action.

Antiviral properties of extract of Opuntia streptacantha.

An extract of the cactus plant Opuntia streptacantha inhibited intracellular virus replication and inactivated extracellular virus. Inhibition of virus replication also occurred following pre-infection treatment--a favourable finding in terms of in-vivo limitation of virus disease. There was inhibition of both DNA and RNA virus replication, for example, herpes simplex virus, equine herpes virus, pseudorabies virus, influenza virus, respiratory syncytial virus and human immunodeficiency virus, with normal protein synthesis in uninfected cells at extract concentrations which were 15-fold in excess of 50% viral inhibitory concentrations (1 mg/ml). The active inhibitory component(s) of the extract appeared to be protein in nature and resided mainly in the wall of the plant rather than in the cuticle or inner sap. The extract was non-toxic on oral administration to mice, horses and human patients; the non-toxicity of intravenous administration of 70 mg to a mouse representing at least fifty tissue culture 50% viral inhibitory dosages encourages clinical trial of this extract in virus disease of human and veterinary species.