Browsing by Subject "ANTIVIRAL ACTIVITY"

Sort by: Order: Results:

Now showing items 1-7 of 7
  • Hemilä, Harri; Chalker, Elizabeth (2021)
    In this individual patient data meta-analysis we examined datasets of two randomized placebo-controlled trials which investigated the effect of nasal carrageenan separately on children and adults. In both trials, iota-carrageenan was administered nasally three times per day for 7 days for patients with the common cold and follow-up lasted for 21 days. We used Cox regression to estimate the effect of carrageenan on recovery rate. We also used quantile regression to calculate the effect of carrageenan on colds of differing lengths. Nasal carrageenan increased the recovery rate from all colds by 54% (95% CI 15%-105%; p = .003). The increase in recovery rate was 139% for coronavirus infections, 119% for influenza A infections, and 70% for rhinovirus infections. The mean duration of all colds in the placebo groups of the first four quintiles were 4.0, 6.8, 8.8, and 13.7 days, respectively. The fifth quintile contained patients with censored data. The 13.7-day colds were shortened by 3.8 days (28% reduction), and 8.8-day colds by 1.3 days (15% reduction). Carrageenan had no meaningful effect on shorter colds. In the placebo group, 21 patients had colds lasting over 20 days, compared with six patients in the carrageenan group, which corresponds to a 71% (p = .003) reduction in the risk of longer colds. Given that carrageenan has an effect on diverse virus groups, and effects at the clinical level on two old coronaviruses, it seems plausible that carrageenan may have an effect on COVID-19. Further research on nasal iota-carrageenan is warranted.
  • Das, Pratyush Kumar; Puusepp, Laura; Varghese, Finny S.; Utt, Age; Ahola, Tero; Kananovich, Dzmitry G.; Lopp, Margus; Merits, Andres; Karelson, Mati (2016)
    Chikungunya virus (CHIKV; genus Alphavirus) is the causative agent of chikungunya fever. CHIKV replication can be inhibited by some broad-spectrum antiviral compounds; in contrast, there is very little information about compounds specifically inhibiting the enzymatic activities of CHIKV replication proteins. These proteins are translated in the form of a nonstructural (ns) P1234 polyprotein precursor from the CHIKV positive-strand RNA genome. Active forms of replicase enzymes are generated using the autoproteolytic activity of nsP2. The available three-dimensional (3D) structure of nsP2 protease has made it a target for in silico drug design; however, there is thus far little evidence that the designed compounds indeed inhibit the protease activity of nsP2 and/or suppress CHIKV replication. In this study, a set of 12 compounds, predicted to interact with the active center of nsP2 protease, was designed using target-based modeling. The majority of these compounds were shown to inhibit the ability of nsP2 to process recombinant protein and synthetic peptide substrates. Furthermore, all compounds found to be active in these cell-free assays also suppressed CHIKV replication in cell culture, the 50% effective concentration (EC50) of the most potent inhibitor being similar to 1.5 mu M. Analysis of stereoisomers of one compound revealed that inhibition of both the nsP2 protease activity and CHIKV replication depended on the conformation of the inhibitor. Combining the data obtained from different assays also indicates that some of the analyzed compounds may suppress CHIKV replication using more than one mechanism.
  • 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.
  • Soderholm, Sandra; Fu, Yu; Gaelings, Lana; Belanov, Sergey; Yetukuri, Laxma; Berlinkov, Mikhail; Cheltsov, Anton V.; Anders, Simon; Aittokallio, Tero; Nyman, Tuula A.; Matikainen, Sampsa; Kainov, Denis E. (2016)
    Human influenza A viruses (IAVs) cause global pandemics and epidemics. These viruses evolve rapidly, making current treatment options ineffective. To identify novel modulators of IAV-host interactions, we re-analyzed our recent transcriptomics, metabolomics, proteomics, phosphoproteomics, and genomics/virtual ligand screening data. We identified 713 potential modulators targeting 199 cellular and two viral proteins. Anti-influenza activity for 48 of them has been reported previously, whereas the antiviral efficacy of the 665 remains unknown. Studying anti-influenza efficacy and immuno/neuro-modulating properties of these compounds and their combinations as well as potential viral and host resistance to them may lead to the discovery of novel modulators of IAV-host interactions, which might be more effective than the currently available anti-influenza therapeutics.
  • Bakour, Meryem; Laaroussi, Hassan; Ousaaid, Driss; El Ghouizi, Asmae; Es-safi, Imane; Mechchate, Hamza; Lyoussi, Badiaa (2022)
    The coronavirus disease 2019 (COVID-19) is an epidemic caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Populations at risk as well as those who can develop serious complications are people with chronic diseases such as diabetes, hypertension, and the elderly. Severe symptoms of SARS-CoV-2 infection are associated with immune failure and dysfunction. The approach of strengthening immunity may be the right choice in order to save lives. This review aimed to provide an overview of current information revealing the importance of bee products in strengthening the immune system against COVID-19. We highlighted the immunomodulatory and the antiviral effects of zinc and polyphenols, which may actively contribute to improving symptoms and preventing complications caused by COVID-19 and can counteract viral infections. Thus, this review will pave the way for conducting advanced experimental research to evaluate zinc and polyphenols-rich bee products to prevent and reduce the severity of COVID-19 symptoms.
  • Zhang, Yuezhou; Xhaard, Henri; Ghemtio, Leo (2018)
    Betulin derivatives have been proven effective in vitro against Leishmania donovani amastigotes, which cause visceral leishmaniasis. Identifying the molecular targets and molecular mechanisms underlying their action is a currently an unmet challenge. In the present study, we tackle this problem using computational methods to establish properties essential for activity as well as to screen betulin derivatives against potential targets. Recursive partitioning classification methods were explored to develop predictive models for 58 diverse betulin derivatives inhibitors of L. donovani amastigotes. The established models were validated on a testing set, showing excellent performance. Molecular fingerprints FCFP_6 and ALogP were extracted as the physicochemical properties most extensively involved in separating inhibitors from non-inhibitors. The potential targets of betulin derivatives inhibitors were predicted by in silico target fishing using structure-based pharmacophore searching and compound-pharmacophore-targetpathway network analysis, first on PDB and then among L. donovani homologs using a PSI-BLAST search. The essential identified proteins are all related to protein kinase family. Previous research already suggested members of the cyclin-dependent kinase family and MAP kinases as Leishmania potential drug targets. The PSI-BLAST search suggests two L. donovani proteins to be especially attractive as putative betulin target, heat shock protein 83 and membrane transporter D1.
  • Ianevski, Aleksandr; Yao, Rouan; Zusinaite, Eva; Lello, Laura Sandra; Wang, Sainan; Jo, Eunji; Yang, Jaewon; Ravlo, Erlend; Wang, Wei; Lysvand, Hilde; Loseth, Kirsti; Oksenych, Valentyn; Tenson, Tanel; Windisch, Marc P.; Poranen, Minna M.; Nieminen, Anni I.; Nordbo, Svein Arne; Fenstad, Mona Hoysaeter; Grodeland, Gunnveig; Aukrust, Pal; Troseid, Marius; Kantele, Anu; Lastauskiene, Egle; Vitkauskiene, Astra; Legrand, Nicolas; Merits, Andres; Bjoras, Magnar; Kainov, Denis E. (2021)
    Background: There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects. Methods: Here, we tested the antiviral properties of interferons (IFNs), alone and with other drugs in vitro. Results: While IFNs alone were insufficient to completely abolish replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), IFN alpha, in combination with remdesivir, EIDD-2801, camostat, cycloheximide, or convalescent serum, proved to be more effective. Transcriptome and metabolomic analyses revealed that the IFN alpha-remdesivir combination suppressed SARS-CoV-2-mediated changes in Calu-3 cells and lung organoids, although it altered the homeostasis of uninfected cells and organoids. We also demonstrated that IFN alpha combinations with sofosbuvir, telaprevir, NITD008, ribavirin, pimodivir, or lamivudine were effective against HCV, HEV, FLuAV, or HIV at lower concentrations, compared to monotherapies. Conclusions: Altogether, our results indicated that IFN alpha can be combined with drugs that affect viral RNA transcription, protein synthesis, and processing to make synergistic combinations that can be attractive targets for further pre-clinical and clinical development against emerging and re-emerging viral infections.