Antiviral Metal Complexes

The initial events (virus adsorption and fusion with the cells) in the replicative cycle of human immunodeficiency virus (HIV) can serve as targets for the antiviral action of metal-binding compounds such as polyanionic compounds (polysulfates, polysulfonates, polycarboxylates, polyoxometalates, and sulfonated or carboxylated metalloporphyrins), bicyclams and G-octet-forming oligonucleotides. The adsorption and fusion of HIV with its target cells depends on the interaction of the viral envelope glycoproteins (gp 120) with the receptors (CD4, CXCR4) at the outer cell membrane. We are currently investigating how the aforementioned compounds interfere with these viral glycoproteins and/or cell receptor

The impact of concentrated pig production in Flanders : a spatial analysis

Historically concentrated livestock production and, consequently, manure production and management in Belgium have resulted in severe environmental impacts. One major impact, nitrate leaching from soil to surface water, is being tackled through the European Nitrates Directive by imposing strict fertilization standards. However, another significant impact of manure management is the emission of greenhouse gasses (GHG - CO2, CH4, NH3 and N2O) into the air, thereby contributing to global warming. Calls have been made to reduce the high manure pressure and related environmental effects in Belgium by relocating and more evenly spreading livestock production. This paper explores the spatial spreading of CO2-equivalent emissions from livestock production in Belgium and attempt to answer the following question: ‘Can spatial reallocation of livestock production in Belgium reduce the impact of GHG emissions?’. This question is translated into several research objectives: 1) conduct an economic (cost minimization) and environmental (GHG minimization) optimization for 3 manure management scenarios, 2) determine the main differences between both approaches, and 3) determine the marginal spatial impact on CO2 emissions of a decrease in manure pressure (i.e., increased spreading of pig production). To conduct the analysis, a model was developed that builds on the spatial mathematical programming multi-agent manure allocation model developed by Van der Straeten et al. (2010). Three options for manure management are inserted: transport of raw manure from nutrient excess to nutrient deficit areas, biological treatment of manure (manure processing) and manure separation. The model optimizes, at municipal level, either the cost-efficiency, either the environmental effect of the manure market in Belgium based on Belgian fertilization standards. While cost-efficiency is calculated based on transport distances and cost of manure separation and processing, GHG emissions, and hence, carbon footprint, are determined based on a life cycle analysis type calculation. The results of the model simulations show that, while the economic optimum is reached by maximizing the transport of raw manure until fertilization standards are fulfilled and subsequently separating and processing the excess manure, the environmental optimum, from a carbon footprint point of view, is reached by separating all manure as this option has the lowest CO2 emissions, mainly due to the limited manure storage time. Moreover, the analyses indicate that rearrangement of the spatial spreading of livestock production in Belgium will not substantially decrease CO2 emissions. As manure storage is the main contributor to the carbon footprint, solutions should rather lie in changing these storage systems

Historical Perspectives in the Development of Antiviral Agents Against Poxviruses

The poxvirus vaccinia virus (VV) served as the model virus for which the first antivirals, the thiosemicarbazones, were identified. This dates back to 1950; and, although there is at present no single antiviral drug specifically licensed for the chemotherapy or -prophylaxis of poxvirus infections, numerous candidate compounds have been described over the past 50 years. These compounds include interferon and inducers thereof (i.e., polyacrylic acid), 5-substituted 2’-deoxyuridines (i.e., idoxuridine), IMP dehydrogenase inhibitors, S-adenosylhomocysteine hydrolase inhibitors, acyclic nucleoside phosphonates (such as cidofovir) and alkoxyalkyl prodrugs thereof (such as CMX001), viral egress inhibitors (such as tecovirimat), and cellular kinase inhibitors (such as imatinib)

Welcome Home: Exploring Housing Options for Adults with Developmental Disabilities in Maine

This poster describes various housing options offering varying levels of supports for adults living with developmental disabilities in Maine. It also provides information for housing options in other states.https://digitalcommons.library.umaine.edu/ccids_posters/1036/thumbnail.jp

Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in mice

BACKGROUND: Viral replication as well as an immunopathological component are assumed to be involved in the development of coxsackie B virus (CBV)-induced myocarditis. We observed that mycophenolic acid (MPA), the active metabolite of the immunosuppressive agent mycophenolate mofetil (MMF), inhibits coxsackie B3 virus (CBV3) replication in primary Human myocardial fibroblasts. We therefore studied whether MMF, which is thus endowed with a direct antiviral as well as immunosuppressive effect, may prevent CBV-induced myocarditis in a murine model. RESULTS: Four week old C3H-mice were infected with CBV3 and received twice daily, for 7 consecutive days (from one day before to 5 days post-virus inoculation) treatment with MMF via oral gavage. Treatment with MMF resulted in a significant reduction in the development of CBV-induced myocarditis as assessed by morphometric analysis, i.e. 78% reduction when MMF was administered at 300 mg/kg/day (p < 0.001), 65% reduction at 200 mg/kg/day (p < 0.001), and 52% reduction at 100 mg/kg/day (p = 0.001). The beneficial effect could not be ascribed to inhibition of viral replication since titers of infectious virus and viral RNA in heart tissue were increased in MMF-treated animals as compared to untreated animals. CONCLUSION: The immunosuppressive agent MMF results in an important reduction of CBV3-induced myocarditis in a murine model

Economic and ecologic assessment of concentrated manure production in Flanders

Manure management causes a big environmental problem in most European regions such as Flanders (Belgium) as it is associated with nutrient surpluses and large amounts of greenhouse gas emissions. In this research, the influence of spatial spreading of livestock production in Belgium and the effect of an open "manure border" between Flanders and Wallonia on greenhouse gas emissions coming from manure management is investigated

Establishment of a novel CCR5 and CXCR4 expressing CD4(+ )cell line which is highly sensitive to HIV and suitable for high-throughput evaluation of CCR5 and CXCR4 antagonists

BACKGROUND: CCR5 and CXCR4 are the two main coreceptors essential for HIV entry. Therefore, these chemokine receptors have become important targets in the search for anti-HIV agents. Here, we describe the establishment of a novel CD4(+ )cell line, U87.CD4.CCR5.CXCR4, stably expressing both CCR5 and CXCR4 at the cell surface. RESULTS: In these cells, intracellular calcium signalling through both receptors can be measured in a single experiment upon the sequential addition of CXCR4- and CCR5-directed chemokines. The U87.CD4.CCR5.CXCR4 cell line reliably supported HIV-1 infection of diverse laboratory-adapted strains and primary isolates with varying coreceptor usage (R5, X4 and R5/X4) and allows to investigate the antiviral efficacy of combined CCR5 and CXCR4 blockade. The antiviral effects recorded in these cells with the CCR5 antagonist SCH-C and the CXCR4 antagonist AMD3100 were similar to those noted in the single CCR5- or CXCR4-transfected U87.CD4 cells. Furthermore, the combination of both inhibitors blocked the infection of all evaluated HIV-1 strains and isolates. CONCLUSIONS: Thus, the U87.CD4.CCR5.CXCR4 cell line should be useful in the evaluation of CCR5 and CXCR4 antagonists with therapeutic potential and combinations thereof

Design and Synthesis of Hydroxyferroquine Derivatives with Antimalarial and Antiviral Activities

Three ferroquine (FQ) derivatives, closely mimicking the antimalarial drug hydroxychloroquine (HCQ), have been prepared. Whereas these organometallic compounds provide the expected reduced cytotoxic effects compared to FQ, they inhibit in vitro growth of Plasmodium falciparum far better than chloroquine (CQ). Moreover, this new class of bioorganometallic compounds exert antiviral effects with some selectivity toward SARS-CoV infection. These new drugs may offer an interesting alternative for Asia where SARS originated and malaria has remained endemic