| 1. |
- Bulgarin, Hanna, et al.
(författare)
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Enhanced and copper concentration dependent virucidal effect against SARS-CoV-2 of electrospun poly(vinylidene difluoride) filter materials
- 2024
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 27:6
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Tidskriftsartikel (refereegranskat)abstract
- Virucidal filter materials were prepared by electrospinning a solution of 28 wt % poly(vinylidene difluoride) in N,N-dimethylacetamide without and with the addition of 0.25 wt %, 0.75 wt %, 2.0 wt %, or 3.5 wt % Cu(NO3)2 · 2.5H2O as virucidal agent. The fabricated materials had a uniform and defect free fibrous structure and even distribution of copper nanoclusters. X-ray diffraction analysis showed that during the electrospinning process, Cu(NO3)2 · 2.5H2O changed into Cu2(NO3)(OH)3. Electrospun filter materials obtained by electrospinning were essentially macroporous. Smaller pores of copper nanoclusters containing materials resulted in higher particle filtration than those without copper nanoclusters. Electrospun filter material fabricated with the addition of 2.0 wt % and 3.5 wt % of Cu(NO3)2 · 2.5H2O in a spinning solution showed significant virucidal activity, and there was 2.5 ± 0.35 and 3.2 ± 0.30 logarithmic reduction in the concentration of infectious SARS-CoV-2 within 12 h, respectively. The electrospun filter materials were stable as they retained virucidal activity for three months.
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| 2. |
- Allas, Ular, et al.
(författare)
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Antibacterial activity of the nitrovinylfuran G1 (Furvina) and its conversion products
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- 2-Bromo-5-(2-bromo-2-nitrovinyl) furan (G1 or Furvina) is an antimicrobial with a direct reactivity against thiol groups. It is active against Gram-positive and Gram-negative bacteria, yeasts and filamentous fungi. By reacting with thiol groups it causes direct damage to proteins but, as a result, is very short-living and interconverts into an array of reaction products. Our aim was to characterize thiol reactivity of G1 and its conversion products and establish how much of antimicrobial and cytotoxic effects are due to the primary activity of G1 and how much can be attributed to its reaction products. Stability of G1 in growth media as well as its conversion in the presence of thiols was characterized. The structures of G1 decomposition products were determined using NMR and mass-spectroscopy. Concentration-and time-dependent killing curves showed that G1 is bacteriostatic for Escherichia coli at the concentration of 16 mu g/ml and bactericidal at 32 mu g/ml. However, G1 is inefficient against non-growing E. coli. Addition of cysteine to medium reduces the antimicrobial potency of G1. Nevertheless, the reaction products of G1 and cysteine enabled prolonged antimicrobial action of the drug. Therefore, the activity of 2-bromo-5-(2-bromo-2-nitrovinyl) furan is a sum of its immediate reactivity and the antibacterial effects of the conversion products.
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| 3. |
- Bösl, Korbinian, et al.
(författare)
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Common Nodes of Virus-Host Interaction Revealed Through an Integrated Network Analysis
- 2019
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.
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| 4. |
- Ianevski, Aleksandr, et al.
(författare)
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Low Temperature and Low UV Indexes Correlated with Peaks of Influenza Virus Activity in Northern Europe during 2010-2018
- 2019
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- With the increasing pace of global warming, it is important to understand the role of meteorological factors in influenza virus (IV) epidemics. In this study, we investigated the impact of temperature, UV index, humidity, wind speed, atmospheric pressure, and precipitation on IV activity in Norway, Sweden, Finland, Estonia, Latvia and Lithuania during 2010-2018. Both correlation and machine learning analyses revealed that low temperature and UV indexes were the most predictive meteorological factors for IV epidemics in Northern Europe. Our in vitro experiments confirmed that low temperature and UV radiation preserved IV infectivity. Associations between these meteorological factors and IV activity could improve surveillance and promote development of accurate predictive models for future influenza outbreaks in the region.
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| 5. |
- Ianevski, Aleksandr, et al.
(författare)
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Novel activities of safe-in-human broad-spectrum antiviral agents
- 2018
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Ingår i: Antiviral Research. - : Elsevier. - 0166-3542 .- 1872-9096. ; 154, s. 174-182
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Tidskriftsartikel (refereegranskat)abstract
- According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-inhuman antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley fever virus. Thus, the spectrum of antiviral activities of existing antiviral agents could be expanded towards other viral diseases.
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| 6. |
- Martikainen, Miika, et al.
(författare)
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IFN-I-tolerant oncolytic Semliki Forest virus in combination with anti-PD1 enhances T cell response against mouse glioma
- 2021
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Ingår i: MOLECULAR THERAPY-ONCOLYTICS. - : Cell Press. - 2372-7705. ; 21, s. 37-46
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Tidskriftsartikel (refereegranskat)abstract
- Oncolytic virotherapy holds promise of effective immunotherapy against otherwise nonresponsive cancers such as glioblastoma. Our previous findings have shown that although oncolytic Semliki Forest virus (SFV) is effective against various mouse glioblastoma models, its therapeutic potency is hampered by type I interferon (IFN-I)-mediated antiviral signaling. In this study, we constructed a novel IFN-I-resistant SFV construct, SFV-AM6, and evaluated its therapeutic potency in vitro, ex vivo, and in vivo in the IFN-I competent mouse GL261 glioma model. In vitro analysis shows that SFV-AM6 causes immunogenic apoptosis in GL261 cells despite high IFN-I signaling. MicroRNA-124 de-targeted SFV-AM6-124T selectively replicates in glioma cells, and it can infect orthotopic GL261 gliomas when administered intraperitoneally. The combination of SFV-AM6-124T and anti-programmed death 1 (PD1) immunotherapy resulted in increased immune cell infiltration in GL261 gliomas, including an increased tumor-reactive CD8(+) fraction. Our results show that SFV-AM6-124T can overcome hurdles of innate anti-viral signaling. Combination therapy with SFV-AM6-124T and antiPD1 promotes the inflammatory response and improves the immune microenvironment in the GL261 glioma model.
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| 7. |
- Paern, Kalle, et al.
(författare)
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Transfection of Infectious RNA and DNA/RNA Layered Vectors of Semliki Forest Virus by the Cell-Penetrating Peptide Based Reagent PepFect6
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Viral vectors have a wide variety of applications ranging from fundamental studies of viruses to therapeutics. Recombinant viral vectors are usually constructed using methods of reverse genetics to obtain the genetic material of the viral vector. The physicochemical properties of DNA and RNA make them unable to access cells by themselves, and they require assistance to achieve intracellular delivery. Non-viral delivery vectors can be used for this purpose if they enable efficient intracellular delivery without interfering with the viral life cycle. In this report, we utilize Semliki Forest virus (genus alphavirus) based RNA and DNA vectors to study the transfection efficiency of the non-viral cell-penetrating peptide-based delivery vector PepFect6 in comparison with that of the cationic liposome-based Lipofectamine 2000, and assess their impact on viral replication. The optimal conditions for transfection were determined for both reagents. These results demonstrate, for the first time, the ability of PepFect6 to transport large (13-19 kbp) constructs across the cell membrane. Curiously, DNA molecules delivered using the PepFect6 reagent were found to be transported to the cell nucleus approximately 1.5 hours later than DNA molecules delivered using the Lipofectamine 2000 reagent. Finally, although both PepFect6 and Lipofectamine 2000 reagents can be used for alphavirus research, PepFect6 is preferred because it does not induce changes in the normal cellular phenotype and it does not affect the normal replication-infection cycle of viruses in previously transfected cells.
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| 8. |
- Ramachandran, Mohanraj, 1988-, et al.
(författare)
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Safe and effective treatment of experimental neuroblastoma and glioblastoma using systemically administered triple microRNA-detargeted oncolytic Semliki Forest virus
- 2017
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 23:6, s. 1519-1530
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE:Glioblastoma multiforme (GBM) and high-risk neuroblastoma are cancers with poor outcome. Immunotherapy in the form of neurotropic oncolytic viruses is a promising therapeutic strategy for these malignancies. Here we evaluate the oncolytic potential of the neurovirulent and partly interferon (IFN)-β-resistant Semliki Forest virus (SFV)-4 in GBMs and neuroblastomas. To reduce neurovirulence we constructed SFV4miRT, which is attenuated in normal CNS cells through insertion of microRNA target sequences for miR124, miR125, miR134 Experimental Design:Oncolytic activity of SFV4miRT was examined in mouse neuroblastoma and GBM cell lines and in patient-derived human glioblastoma cell cultures (HGCC). In vivo neurovirulence and therapeutic efficacy was evaluated in two syngeneic orthotopic glioma models (CT-2A, GL261) and syngeneic subcutaneous neuroblastoma model (NXS2). The role of IFN-β in inhibiting therapeutic efficacy was investigated.RESULTS:The introduction of microRNA target sequences reduced neurovirulence of SFV4 in terms of attenuated replication in mouse CNS cells and ability to cause encephalitis when administered intravenously. A single intravenous injection of SFV4miRT prolonged survival and cured 4 of 8 mice (50%) with NXS2 and 3 of 11 mice (27%) with CT-2A, but not for GL261 tumor bearing mice. In vivo therapeutic efficacy in different tumor models inversely correlated to secretion of IFN-β by respective cells upon SFV4 infection in vitro Similarly, killing efficacy of HGCC lines inversely correlated to IFN-β response and interferon-α⁄β receptor (IFNAR)-1 expression.CONCLUSIONS:SFV4miRT has reduced neurovirulence, while retaining its oncolytic potential. SFV4miRT is an excellent candidate for treatment of GBMs and neuroblastomas with low IFN-β secretion.
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| 9. |
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| 10. |
- Viru, Liane, et al.
(författare)
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Novel viral vectors utilizing intron splice-switching to activate genome rescue, expression and replication in targeted cells
- 2011
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Ingår i: Virology Journal. - 1743-422X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: The outcome of virus infection depends from the precise coordination of viral gene expression and genome replication. The ability to control and regulate these processes is therefore important for analysis of infection process. Viruses are also useful tools in bio- and gene technology; they can efficiently kill cancer cells and trigger immune responses to tumors. However, the methods for constructing tissue or cell-type specific viruses typically suffer from low target-cell specificity and a high risk of reversion. Therefore novel and universal methods of regulation of viral infection are also important for therapeutic application of virus-based systems. Methods: Aberrantly spliced introns were introduced into crucial gene-expression units of adenovirus vector and alphavirus DNA/RNA layered vectors and their effects on the viral gene expression, replication and/or the release of infectious genomes were studied in cell culture. Transfection of the cells with splice-switching oligonucleotides was used to correct the introduced functional defect(s). Results: It was demonstrated that viral gene expression, replication and/or the release of infectious genomes can be blocked by the introduction of aberrantly spliced introns. The insertion of such an intron into an adenovirus vector reduced the expression of the targeted gene more than fifty-fold. A similar insertion into an alphavirus DNA/RNA layered vector had a less dramatic effect; here, only the release of the infectious transcript was suppressed but not the subsequent replication and spread of the virus. However the insertion of two aberrantly spliced introns resulted in an over one hundred-fold reduction in the infectivity of the DNA/RNA layered vector. Furthermore, in both systems the observed effects could be reverted by the delivery of splice-switching oligonucleotide(s), which corrected the splicing defects. Conclusions: Splice-switch technology, originally developed for genetic disease therapy, can also be used to control gene expression of viral vectors. This approach represents a novel, universal and powerful method for controlling gene expression, replication, viral spread and, by extension, virus-induced cytotoxic effects and can be used both for basic studies of virus infection and in virus-based gene-and anti-cancer therapy.
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