| 1. |
- Andersen, Petter I., et al.
(författare)
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Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine
- 2019
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Repurposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FLUAV), niclosamide against HSV-2, brequinar against human immunodeficiency virus 1 (HIV-1), and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vitro and in vivo tests.
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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- Ravlo, Erlend, et al.
(författare)
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Boosted production of antibodies which neutralized different SARS-CoV-2 variants in a COVID-19 convalescent following mRNA vaccination - a case study
- 2023
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Ingår i: International Journal of Infectious Diseases. - 1878-3511. ; 137, s. 75-78
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Tidskriftsartikel (refereegranskat)abstract
- Vaccinated convalescents do not develop severe COVID-19 after infection with new SARS-CoV-2 variants. We questioned how mRNA vaccination of convalescents provides protection from emerging virus variant. From the cohort of 71 convalescent plasma donors, we identified a patient who developed immune response to infection with SARS-CoV-2 variant of 20A clade and who subsequently received mRNA vaccine encoding S protein of strain of 19A clade. We showed that vaccination increased the production of immune cells and anti-S antibodies in the serum. Serum antibodies neutralized not only 19A and 20A, but also 20B, 20H, 21J and 21K virus variants. One of the serum antibodies (100F8) completely neutralized 20A, 21J and partially 21K strains. 100F8 was structurally similarly to published Ab188 antibody, which recognized non-conserved epitope on the S protein. We proposed that 100F8 and other serum antibodies of the patient which recognized non- and conserved epitopes of the S protein, could have additive or synergistic effect to neutralize various virus variants. Thus, mRNA vaccination could be beneficial for convalescents because it boosts production of neutralizing antibodies with broad-spectrum activity. -.
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| 6. |
- Yong-Dae, Kwon, 1984-, et al.
(författare)
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N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle
- 2020
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Asparagine (N)-linked protein glycosylation plays an important role in protein synthesis and modification. Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein areN-glycosylated. The prM protein of all ZIKV strains contains a singleN-linked glycosylation site, while not all strains contain an N-linked site in the E protein. Our aim was to examine the impact of prM and E N-linked glycosylation on ZIKV infectivity and cell trafficking. Using a ZIKV infectious clone, we found that when theN-glycan sites were removed, the prM- and the prM/E-double mutants did not produce an infectious virus in the supernatant. Further, by using ZIKV prME constructs, we found thatN-glycosylation was necessary for effective secretion of ZIKV virions. The absence of theN-glycan on prM or E caused protein aggregation in the rough endoplasmatic reticulum (ER) compartment. The aggregation was more pronounced for the prM-mutation, and the mutant virus lost the ER-Golgi intermediate compartment (ERGIC) localization. In addition, lack of theN-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker. To conclude, we show that the prMN-glycan is essential for the ZIKV infectious cycle, and plays an important role in viral protein trafficking, protein folding, and virion assembly.
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