Synthesis and antiviral activity of a novel glycosyl sulfoxide against classical swine fever virus.
A novel compound-2″,3″,4″,6″-tetra-O-acetyl-β-d-galactopyranosyl-(1→4)-2',3',6'-tri-O-acetyl-1-thio-β-d-glucopyranosyl-(5-nitro-2-pyridyl) sulfoxide-designated GP6 was synthesized and assayed for cytotoxicity and in vitro antiviral properties against classical swine fever virus (CSFV) in this study. We showed that the examined compound effectively arrested CSFV growth in swine kidney cells (SK6) at a 50% inhibitory concentration (IC50) of 5 ± 0.12 μg/ml without significant toxicity for mammalian cells. Moreover, GP6 reduced the viral E2 and E(rns) glycoproteins expression in a dose-dependent manner. We have excluded the possibility that the inhibitor acts at the replication step of virus life cycle as assessed by monitoring of RNA level in cells and culture medium of SK6 cells after single round of infection as a function of GP6 treatment. Using recombinant E(rns) and E2 proteins of classical swine fever virus produced in baculovirus expression system we have demonstrated that GP6 did not influence glycoprotein production and maturation in insect cells. In contrast to mammalian glycosylation pathway, insect cells support only the ER-dependent early steps of this process. Therefore, we concluded that the late steps of glycosylation process are probably the main targets of GP6. Due to the observed antiviral effect accompanied by low cytotoxicity, this inhibitor represents potential candidate for the development of antiviral agents for anti-flavivirus therapy. Further experiments are needed for investigating whether this compound can be used as a safe antiviral agent against other viruses from unrelated groups.
Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Kladki 24, 80-822 Gdansk, Poland. Electronic address: ewelina@biotech.ug.gda.pl.
Ewelina
E
Krol
Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 4, 44-101 Gliwice, Poland.
Gabriela
G
Pastuch-Gawolek
Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Kladki 24, 80-822 Gdansk, Poland.
Dawid
D
Nidzworski
Department of Virus Molecular Biology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Kladki 24, 80-822 Gdansk, Poland.
Michal
M
Rychlowski
Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 4, 44-101 Gliwice, Poland.
Wieslaw
W
Szeja
Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland.
Grzegorz
G
Grynkiewicz
Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Kladki 24, 80-822 Gdansk, Poland.
Boguslaw
B
Szewczyk
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006692:Classical Swine Fever Virus / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012451:Safrole / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D013552:Swine; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism
D000998:Antiviral Agents; D006023:Glycoproteins; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D012451:Safrole; C005746:sulfoxide
Classical swine fever virus; Glycoproteins; Sulfoxides