| 1. |
- Berg, Anna-Karin, et al.
(författare)
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Antiviral Treatment of Coxsackie B Virus Infection in Human Pancreatic Islets
- 2007
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Ingår i: Antiviral Research. - : Elsevier BV. - 0166-3542 .- 1872-9096. ; 74:1, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- Enterovirus infections of the pancreatic islets are believed to trigger or precipitate the near total destruction of β-cells that constitutes type 1 diabetes (T1D). This study investigated the ability of an anti-picornaviral compound, pleconaril, to block the replication of two β-cell tropic Coxsackie B4 virus (CBV-4) strains in isolated human islets. The two strains, VD2921 and V89 4557, with demonstrated abilities to cause non-lytic persistence or lytic infection, respectively, in islets, represented two different potential mechanisms behind virus-induced T1D. The virus replication in the islets was studied with and without addition of pleconaril. In addition, islet morphology was studied every day. To test the effects of pleconaril and/or DMSO on the β-cells’ insulin secretion, glucose perifusions were performed on treated and untreated islets. Virus titrations showed a clear reduction of the replication of both strains after pleconaril treatment. The VD2921 strain was inhibited to undetectable levels. The V89 4557 strain, however, showed an initial reduction of titers but virus titers then increased despite the addition of a second dose of pleconaril. This incomplete inhibition of viral replication suggested the existence of a resistant subtype within this strain. Pleconaril treatment reduced the β-cells’ insulin secretion in response to glucose stimulation in some experiments and induced slight morphological changes to the islets compared to untreated controls. In summary, pleconaril reduced the replication of the two β-cell tropic CBV-4 strains in human islets. However, genetic differences between these strains influenced the effectiveness of pleconaril treatment. This stresses the importance of using multiple viral strains in antiviral tests.
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| 2. |
- Coutard, B., et al.
(författare)
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The VIZIER project : Preparedness against pathogenic RNA viruses
- 2008
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Ingår i: Antiviral Research. - : Elsevier BV. - 0166-3542 .- 1872-9096. ; 78:1, s. 37-46
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Tidskriftsartikel (refereegranskat)abstract
- Life-threatening RNA viruses emerge regularly, and often in an unpredictable manner. Yet, the very few drugs available against known RNA viruses have sometimes required decades of research for development. Can we generate preparedness for outbreaks of the, as yet, unknown viruses? The VIZIER (VIral enZymes InvolvEd in Replication) (http://www.vizier-europe.org/) project has been set-up to develop the scientific foundations for countering this challenge to society. VIZIER studies the most conserved viral enzymes (that of the replication machinery, or replicases) that constitute attractive targets for drug-design. The aim of VIZIER is to determine as many replicase crystal structures as possible from a carefully selected list of viruses in order to comprehensively cover the diversity of the RNA virus universe, and generate critical knowledge that could be efficiently utilized to jump-start research on any emerging RNA virus. VIZIER is a multidisciplinary project involving (i) bioinformatics to define functional domains, (ii) viral genomics to increase the number of characterized viral genomes and prepare defined targets, (iii) proteomics to express, purify, and characterize targets, (iv) structural biology to solve their crystal structures, and (v) pre-lead discovery to propose active scaffolds of antiviral molecules.
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| 3. |
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| 4. |
- Johansson, Susanne M C, et al.
(författare)
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Multivalent sialic acid conjugates inhibit adenovirus type 37 from binding to and infecting human corneal epithelial cells
- 2007
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Ingår i: Antiviral Research. - : Elsevier BV. - 0166-3542 .- 1872-9096. ; 73:2, s. 92-100
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Tidskriftsartikel (refereegranskat)abstract
- Adenovirus type 37 is one of the main causative agents of epidemic keratoconjunctivitis. In a series of publications, we have reported that this virus uses sialic acid as a cellular receptor. Here we demonstrate in vitro that on a molar basis, multivalent sialic acid conjugated to human serum albumin prevents adenovirus type 37 from binding to and infecting human corneal epithelial cells 1000-fold more efficiently than monosaccharidic sialic acid. We also demonstrate that the extraordinary inhibitory effect of multivalent sialic acid is due to the ability of this compound to aggregate virions. We conclude that multivalent sialic acid may be a potential new antiviral drug, for use in the treatment of epidemic keratoconjunctivitis caused by the adenoviruses that use sialic acid as cellular receptor.
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| 5. |
- Mistry, Nitesh, et al.
(författare)
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The anti-papillomavirus activity of human and bovine lactoferricin.
- 2007
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Ingår i: Antiviral Research. - : Elsevier BV. - 0166-3542 .- 1872-9096. ; 75:3, s. 258-265
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus (HPV) cause common warts, laryngeal papilloma and genital condylomata and is necessary for the development of cervical cancer. We have previously found that lactoferrin has antiviral activity against HPV-16 and others have demonstrated that lactoferricin, an N-terminal fragment of lactoferrin, has inhibitory activities against several viruses. Two cell lines and two virus types, HPV-5 and HPV-16, were used to study if lactoferrin and lactoferricin could inhibit HPV pseudovirus (PsV) infection. We demonstrated that bovine lactoferrin (bLf) and human lactoferrin (hLf) were both potent inhibitors of HPV-5 and -16 PsV infections. Among the four lactoferricin derivatives we analyzed, a 15 amino acid peptide from bovine lactoferricin (bLfcin) 17-31 was the most potent inhibitor of both HPV-5 and HPV-16 PsV infection. Among the other derivatives, the human lactoferricin (hLfcin) 1-49 showed some antiviral activity against HPV PsV infection while bLfcin 17-42 inhibited only HPV-5 PsV infection in one of the cell lines. When we studied initial attachment of HPV-16, only bLfcin 17-42 and hLfcin 1-49 had an antiviral effect. This is the first time that lactoferricin was demonstrated to have an inhibitory effect on HPV infection and the antiviral activity differed depending on size, charge and structures of the lactoferricin.
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| 6. |
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| 7. |
- Elinder, Malin, et al.
(författare)
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MIV-170 : A novel NNRTI exhibiting tight binding to HIV-1 reverse transcriptase (RT)
- 2008
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Ingår i: Antiviral Research. - : Elsevier BV. - 0166-3542.
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Konferensbidrag (refereegranskat)abstract
- The NNRTI MIV-170 has been found to be a very efficient inhibitor of wtHIV and HIV mutant strains resistant to the NNRTIs used in the clinic. To better understand the interaction between MIV-170 and HIV-1 the details of this have been studied by different methods. The kinetics of the interaction between MIV-170 and HIV-1 RT was analysed using a biosensor assay. The association and dissociation rates were determined using immobilized wtRT or RT mutants and MIV-170 as analyte. The results demonstrated that MIV-170 had both a faster association and a slower dissociation rate than efavirenz, nevirapine and delavirdine, thus exhibiting a higher affinity than these compounds. The strength of the interaction between the NNRTIs and RT and RT mutants in the biosensor assay was compared to the reversibility of inhibition in cell culture experiments. In these experiments virus and infected cells were incubated with MIV-170 and other NNRTIs for various times and after removal of the compounds the remaining infectivity was assayed. X-ray analysis of the binding of MIV-170 to HIV-1 RT displayed extensive interactions, not only between the compound and the lining amino acids but also between these residues, turning the binding cavity into a rigid entity and explaining the tight binding in the biosensor assay and the inactivation of HIV.
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