Browsing by Subject "INFLUENZA"

Sort by: Order: Results:

Now showing items 1-7 of 7
  • Lamut, Andraž; Gjorgjieva, Marina; Naesens, Lieve; Liekens, Sandra; Lillsunde, Katja-Emilia; Tammela, Päivi; Kikelj, Danijel; Tomašič, Tihomir (2020)
    Seasonal or pandemic influenza virus infections are a worldwide health problem requiring antiviral therapy. Since virus resistance to the established neuraminidase inhibitors and novel polymerase inhibitors is growing, new drug targets are needed. Heat shock protein 90 (Hsp90) is associated with several aspects of the influenza virus life cycle, and is considered a relevant host cell target. We report here on a series of benzo[d]thiazole and 4,5,6,7-tetrahydrobenzo [d]thiazole derivatives with robust and selective activities against influenza A (H1N1, H3N2) and influenza B viruses. Two compounds, 1 and 4, have low micromolar EC50 values and show high binding affinities for Hsp90, which suggests that inhibition of Hsp90 is the mechanism underlying their antiviral effects. These compounds represent suitable scaffolds for designing novel Hsp90 inhibitors with favourable activities against influenza virus.
  • Kakkola, L.; Denisova, O. V.; Tynell, J.; Viiliainen, J.; Ysenbaert, T.; Matos, R. C.; Nagaraj, A.; Öhman, Tiina; Kuivanen, S.; Paavilainen, H.; Feng, L.; Yadav, B.; Julkunen, I.; Vapalahti, O.; Hukkanen, V.; Stenman, J.; Aittokallio, T.; Verschuren, E. W.; Ojala, P. M.; Nyman, T.; Saelens, X.; Dzeyk, K.; Kainov, D. E. (2013)
  • Pesälä, Samuli; Virtanen, Mikko J.; Mukka, Milla; Ylilammi, Kimi; Mustonen, Pekka; Kaila, Minna; Helve, Otto (2019)
    Pesälä S, Virtanen MJ, Mukka M, Ylilammi K, Mustonen P, Kaila M, Helve O
  • Herring, Shawn; Oda, Jessica M.; Wagoner, Jessica; Kirchmeier, Delaney; O'Connor, Aidan; Nelson, Elizabeth A.; Huang, Qinfeng; Liang, Yuying; DeWald, Lisa Evans; Johansen, Lisa M.; Glass, Pamela J.; Olinger, Gene G.; Ianevski, Aleksandr; Aittokallio, Tero; Paine, Mary F.; Fink, Susan L.; White, Judith M.; Polyak, Stephen J. (2021)
    Neglected diseases caused by arenaviruses such as Lassa virus (LASV) and filoviruses like Ebola virus (EBOV) primarily afflict resource-limited countries, where antiviral drug development is often minimal. Previous studies have shown that many approved drugs developed for other clinical indications inhibit EBOV and LASV and that combinations of these drugs provide synergistic suppression of EBOV, often by blocking discrete steps in virus entry. We hypothesize that repurposing of combinations of orally administered approved drugs provides effective suppression of arenaviruses. In this report, we demonstrate that arbidol, an approved influenza antiviral previously shown to inhibit EBOV, LASV, and many other viruses, inhibits murine leukemia virus (MLV) reporter viruses pseudotyped with the fusion glycoproteins (GPs) of other arenaviruses (Junin virus (JUNV], lymphocytic choriomeningitis virus (LCMV), and Pichinde virus (PICA). Arbidol and other approved drugs, including aripiprazole, amodiaquine, sertraline, and niclosamide, also inhibit infection of cells by infectious PICV, and arbidol, sertraline, and niclosamide inhibit infectious LASV. Combining arbidol with aripiprazole or sertraline results in the synergistic suppression of LASV and JUNV GP-bearing pseudoviruses. This proof-of-concept study shows that arenavirus infection in vitro can be synergistically inhibited by combinations of approved drugs. This approach may lead to a proactive strategy with which to prepare for and control known and new arenavirus outbreaks.
  • Wolthers, Katja C.; Susi, Petri; Jochmans, Dirk; Koskinen, Janne; Landt, Olfert; Sanchez, Neus; Palm, Kaia; Neyts, Johan; Butcher, Sarah J. (2019)
    Several research groups in Europe are active on different aspects of human picornavirus research. The AIROPico (Academia-Industry R&D Opportunities for Picornaviruses) consortium combined the disciplines of pathogenesis, diagnostics and therapy development in order to fill the gaps in our understanding of how picornaviruses cause human disease and how to combat them. AIROPico was the first EU consortium dedicated to human picornavirus research and development, and has largely accelerated and improved R&D on picornavirus biology, diagnostics and therapy. In this article, we present the progress on pathogenesis, diagnostics and treatment strategy developments for human picornaviruses resulting from the structured, translational research approach of the AIROPico consortium. We here summarize new insights in protection against infection by maternal or cross-protective antibodies, the visualisation of interactions between virus and neutralizing antibodies by cryoEM structural imaging, and the outcomes from a picornavirus-infected human 3D organoid. Progress in molecular detection and a fast typing assay for rhinovirus species are presented, as well as the identification of new compounds potentially interesting as therapeutic compounds.
  • Nguyen, Tu Thi Kha; Ngo, Tue Tri; Tran, Phuc My; Pham, Tam Thi Thanh; Vu, Hang Thi Ty; Nguyen, Ny Thi Han; Thwaites, Guy; Virtala, Anna-Maija K.; Vapalahti, Olli; Baker, Stephen; Van, Tan Le (2020)
    Active surveillance for zoonotic respiratory viruses is essential to inform the development of appropriate interventions and outbreak responses. Here we target individuals with a high frequency of animal exposure in Vietnam. Three-year community-based surveillance was conducted in Vietnam during 2013-2016. We enrolled a total of 581 individuals (animal-raising farmers, slaughterers, animal-health workers, and rat traders), and utilized reverse transcription-polymerase chain reaction to detect 15 common respiratory viruses in pooled nasal-throat swabs collected at baseline or acute respiratory disease episodes. A respiratory virus was detected in 7.9% (58 of 732) of baseline samples, and 17.7% (136 of 770) of disease episode samples (P <.001), with enteroviruses (EVs), rhinoviruses and influenza A virus being the predominant viruses detected. There were temporal and spatial fluctuations in the frequencies of the detected viruses over the study period, for example, EVs and influenza A viruses were more often detected during rainy seasons. We reported the detection of common respiratory viruses in individuals with a high frequency of animal exposure in Vietnam, an emerging infectious disease hotspot. The results show the value of baseline/control sampling in delineating the causative relationships and have revealed important insights into the ecological aspects of EVs, rhinoviruses and influenza A and their contributions to the burden posed by respiratory infections in Vietnam.
  • Hemila, Harri (2016)
    Background: Vitamin E has influenced the immune system in laboratory studies. Dozens of animal experiments have found that vitamin E offered protection against infections caused by viruses and bacteria. Previously, significant heterogeneity was found in the effect of vitamin E supplementation on pneumonia in humans. The aim of this study was to examine how the effect of vitamin E on pneumonia risk depends on age. Methods: Secondary analysis of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study in Finland, 1985-1993, was performed. Participants were male smokers aged 50-69 years at the baseline who started to smoke at >= 21 years (N=7,469). Intervention was 50 mg/d of vitamin E for 5-8 years. The outcome was the incidence of hospital-treated, community-acquired pneumonia by the age at the follow-up. Results: Among 2,216 participants who smoked 5-19 cigarettes per day at baseline and exercised at leisure time, vitamin E supplementation reduced the incidence of pneumonia by 69% (95% confidence interval [CI]: 43%-83%; 57 pneumonia cases). In this subgroup, vitamin E prevented pneumonia in 12.9% of participants by the age of 74 years. Among 5,253 participants who smoked >= 20 cigarettes per day at baseline or did not exercise, the incidence of pneumonia was 14% lower in the vitamin E participants (95% CI: -38% to +21%; 139 cases). One-third of the participants quit smoking for a period, of whom 27 got pneumonia. The incidence of pneumonia was 72% (95% CI: 31%-89%) lower in the vitamin E group, and this benefit was also seen among those males who smoked >20 cigarettes per day at baseline or did not exercise. Conclusion: Although the evidence of benefit from vitamin E against pneumonia in elderly males is strong in this analysis, the overall findings about vitamin E have been complex. Further research on vitamin E in nonsmoking elderly males is warranted.