Serious outbreaks of severe acute respiratory syndrome (SARS), caused by the newly discovered coronavirus SARS-CoV, occurred between late 2002 and early 2003 and there is an urgent need for effective antiviral agents. RNA interference in animals and post-transcriptional gene silencing plants is mediated by small double-stranded RNA molecules named small interfering RNA (siRNA). Recently, siRNA-induced RNA interference(RNAi) may provide a new approach to therapy for pathogenic viruses, e.g. HIV and HCV. In this study, the silencing potential of seven synthetic siRNAs against SARS-CoV leader, TRS, 3'-UTR and Spike coding sequence have been applied to explore the possibility for prevention of SARS-CoV infection. We demonstrate that siRNAs directed against Spike sequences and the 3'-UTR can inhibit the replication of SARS-CoV in Vero-E6 cells, and holds out promise for the development of an effective antiviral agent against SARS-CoV.

Sargassum hemiphyllum , a kind of brown seaweed generally found along coastlines in East Asia, has long served as a traditional Chinese medicine. S. hemiphyllum has shown an anti-inflammatory effect; however, its mechanism has not been elucidated clearly. This study explored S. hemiphyllum for its biomedical effects. S. hemiphyllum sulfated polysaccharide extract (SHSP) was first prepared; the mouse macrophage cell line (RAW 264.7) activated by lipopolysaccharide (LPS) was used as a model system. The secretion profiles of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α, and NO, were found significantly to be reduced in 1-5 mg/mL dose ranges of SHSP treatments. RT-PCR analysis suggested SHSP inhibits the LPS-induced mRNA expressions of IL-β, iNOS, and COX-2 in a dose-dependent manner. At protein levels, Western blot analysis demonstrated a similar result for NF-κB (p65) in cytosol/nuclear. Taken together, the anti-inflammatory properties of SHSP may be attributed to the down-regulation of NF-κB in nucleus.

Viperin is identified as an antiviral protein induced by interferon (IFN), viral infections, and pathogenassociated molecules. In this study, we found that viperin is highly induced at the RNA level by Japanese encephalitis virus (JEV) and Sindbis virus (SIN) and that viperin protein is degraded in JEV-infected cells through a proteasome-dependent mechanism. Promoter analysis revealed that SIN induces viperin expression in an IFN-dependent manner but that JEV by itself activates the viperin promoter through IFN regulatory factor-3 and AP-1. The overexpression of viperin significantly decreased the production of SIN, but not of JEV, whereas the proteasome inhibitor MG132 sustained the protein level and antiviral effect of viperin in JEVinfected cells. Knockdown of viperin expression by RNA interference also enhanced the replication of SIN, but not that of JEV. Our results suggest that even though viperin gene expression is highly induced by JEV, it is negatively regulated at the protein level to counteract its antiviral effect. In contrast, SIN induces viperin through the action of IFN, and viperin exhibits potent antiviral activity against SIN.Viperin, an interferon (IFN)-induced cellular antiviral protein, was identified originally as cig5 in human cytomegalovirus (HCMV)-infected human fibroblasts (53). A similar gene called vig-1 was identified subsequently in viral hemorrhagic septicemia virus-infected rainbow trout leukocytes (3) and in mouse dendritic cells infected with vesicular stomatitis virus (VSV) and pseudorabies virus (4). Viperin was then found to be induced by both type I and type II IFN and to exhibit antiviral activity against HCMV (9). Furthermore, the results of several gene-profiling microarray studies showed that the viperin gene is one of those that is highly induced by a range of different viruses (20,25,38,40,42,46) and microbial products, such as lipopolysaccharide (35,42), the double-stranded RNA analog poly(I-C) (39), and double-stranded B-form DNA (22), in various cell types.The human viperin gene encodes a protein of 361 amino acids with a predicted molecular mass of 42.2 kDa. Protein sequence analysis reveals a CX 3 CX 2 C motif, which is found in the superfamily of S-adenosyl methionine (SAM)-dependent radical enzymes (44) in residues 83 to 90 of human viperin. Thus, viperin is also called radical SAM domain-containing 2 (RSAD2). The radical SAM superfamily comprises more than 600 members (44, 47), and evidence suggests that the three conserved cysteine residues are part of an unusual iron-sulfur cluster that uses SAM as a cofactor to form a radical that is involved in catalysis (19,27). Although the precise function of viperin remains to be elucidated, recent data have proven its cellular antiviral effects. The overexpression of viperin reduces productive HCMV infection in human fibroblasts by downregulating several structural proteins that are critical for viral assembly and maturation (9), inhibits influenza virus release by perturbing lipid rafts (48), decreases human hepatitis...

Fucoidan, a heparin-like sulfated polysaccharide, is rich in brown algae. It has a wide assortment of protective activities against cancer, for example, induction of hepatocellular carcinoma senescence, induction of human breast and colon carcinoma apoptosis, and impediment of lung cancer cells migration and invasion. However, the anti-metastatic mechanism that fucoidan exploits remains elusive. In this report, we explored the effects of fucoidan on cachectic symptoms, tumor development, lung carcinoma cell spreading and proliferation, as well as expression of metastasis-associated proteins in the Lewis lung carcinoma (LLC) cells-inoculated mice model. We discovered that administration of fucoidan has prophylactic effects on mitigation of cachectic body weight loss and improvement of lung masses in tumor-inoculated mice. These desired effects are attributed to inhibition of LLC spreading and proliferation in lung tissues. Fucoidan also down-regulates expression of matrix metalloproteinases (MMPs), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and vascular endothelial growth factor (VEGF). Moreover, the tumor-bearing mice supplemented with fucoidan indeed benefit from an ensemble of the chemo-phylacticity. The fact is that fucoidan significantly decreases viability, migration, invasion, and MMPs activities of LLC cells. In summary, fucoidan is suitable to act as a chemo-preventative agent for minimizing cachectic symptoms as well as inhibiting lung carcinoma metastasis through down-regulating metastatic factors VEGF and MMPs.

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Japanese encephalitis virus (JEV), a neurotropic flavivirus, is one of the major causes of acute encephalitis in humans. After infection, inflammatory reactions and neurological diseases often develop. Still there are no effective drugs available against virus infection. Recently, extracts of algae have been shown to possess a broad range of biological activities including antivirus activity. In this study, we identified that the sulfated polysaccharide extracts from Ulva lactuca can inhibit JEV infection in Vero cells. Mechanistic studies further revealed that the Ulva sulfated polysaccharide extracts can block virus adsorption and thus make the virus unable to enter cells. The Ulva sulfated polysaccharide extracts also effectively decrease the production of pro-inflammatory cytokines in the JEV-infected primary mixed glia cells. In an animal study, the JEV-infected C3H/HeN mice appeared to have neurobehavioral abnormalities on the fifth day and died on the seventh day post infection. However, the JEV-infected mice pretreated with the Ulva sulfated polysaccharide extracts can delay the onset of hind limb paralysis and thereby prevent mice from death.