title: Immuno-modulating properties of saliphenylhalamide, SNS-032, obatoclax, and gemcitabine.
abstract: Influenza A viruses (IAVs) impact the public health and global economy by causing yearly epidemics and occasional pandemics. Several anti-IAV drugs are available and many are in development. However, the question remains which of these antiviral agents may allow activation of immune responses and protect patients against co- and re-infections. To answer to this question, we analysed immuno-modulating properties of the antivirals saliphenylhalamide (SaliPhe), SNS-032, obatoclax, and gemcitabine, and found that only gemcitabine did not impair immune responses in infected cells. It also allowed activation of innate immune responses in lipopolysaccharide (LPS)- and interferon alpha (IFNα)-stimulated macrophages. Moreover, immuno-mediators produced by gemcitabine-treated IAV-infected macrophages were able to prime immune responses in non-infected cells. Thus, we identified an antiviral agent which might be beneficial for treatment of patients with severe viral infections.
authors.affiliation: Institute of Biotechnology, University of Helsinki, Finland; Finnish Institute of Occupational Health (TTL), Helsinki, Finland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Söderholm
authors.affiliation: The Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Anastasina
authors.affiliation: The Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Finland.
authors.forename: Mohammad Majharul
authors.initials: MM
authors.lastname: Islam
authors.affiliation: National Institute for Health and Welfare (THL), Helsinki, Finland.
authors.forename: Janne
authors.initials: J
authors.lastname: Tynell
authors.affiliation: Department of Biosciences, University of Helsinki, Finland.
authors.forename: Minna M
authors.initials: MM
authors.lastname: Poranen
authors.affiliation: Institute of Biotechnology, University of Helsinki, Finland; Department of Biosciences, University of Helsinki, Finland.
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Bamford
authors.affiliation: Minerva Foundation Institute for Medical Research, Helsinki, Finland.
authors.forename: Jakob
authors.initials: J
authors.lastname: Stenman
authors.affiliation: National Institute for Health and Welfare (THL), Helsinki, Finland; Department of Virology, University of Turku, Turku, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Julkunen
authors.affiliation: Department of Environmental Research, Siauliai University, Siauliai, Lithuania.
authors.forename: Ingrida
authors.initials: I
authors.lastname: Šaulienė
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, USA.
authors.forename: Jef K
authors.initials: JK
authors.lastname: De Brabander
authors.affiliation: Finnish Institute of Occupational Health (TTL), Helsinki, Finland.
authors.forename: Sampsa
authors.initials: S
authors.lastname: Matikainen
authors.affiliation: Institute of Biotechnology, University of Helsinki, Finland.
authors.forename: Tuula A
authors.initials: TA
authors.lastname: Nyman
authors.affiliation: Medical Biotechnology Center, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Xavier
authors.initials: X
authors.lastname: Saelens
authors.affiliation: The Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Finland; Department of Virology, University of Turku, Turku, Finland. Electronic address: denis.kainov@helsinki.fi.
authors.forename: Denis
authors.initials: D
authors.lastname: Kainov
mesh_terms: D000577:Amides / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D060085:Coinfection / Q000188:drug therapy / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology*; D007211:Indoles; D009980:Influenza A virus / Q000187:drug effects / Q000502:physiology; D007251:Influenza, Human / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D016898:Interferon-alpha / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000821:virology*; D010080:Oxazoles / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D012367:RNA, Viral / Q000096:biosynthesis; D012459:Salicylates / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology; D000093542:Gemcitabine
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D016207:Cytokines; D007155:Immunologic Factors; D007211:Indoles; D016898:Interferon-alpha; D008070:Lipopolysaccharides; C484864:N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide; D010080:Oxazoles; D010750:Phosphoproteins; D011758:Pyrroles; D012367:RNA, Viral; D012459:Salicylates; D013844:Thiazoles; C574373:saliphenylhalamide; D003841:Deoxycytidine; C520962:obatoclax; D000093542:Gemcitabine
keywords: Antiviral agents; Immune responses; Influenza A virus; Innate immunity; Virus-host interaction