Synthesis and antiviral activity of a novel glycosyl sulfoxide against classical swine fever virus

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• 作者：Ewelina Krol^a ; ^{ewelina@biotech.ug.gda.pl" class="auth_mail} ; Gabriela Pastuch-Gawolek^b ; Dawid Nidzworski^a ; Michal Rychlowski^c ; Wieslaw Szeja^b ; Grzegorz Grynkiewicz^d ; Boguslaw Szewczyk^a
• 关键词：CC50 ; concentration of the compound required to reduce cell viability by 50% ; CSF ; classical swine fever ; CSFV ; classical swine fever virus ; Ct ; cycle threshold ; ER ; endoplasmic reticulum ; GTs ; glycosyltransferases ; IC50 ; concentration of the compound required to reduce virus plaque formation by 50% ; IPMA ; immunoperoxidase monolayer assay ; MOI ; multiplicity of infection ; PRV ; pseudorabies virus ; Sf9 ; Spodoptera frugiperda insect cell line ; SD ; standard deviations ; S.I. ; selectivity index ; SK6 ; s
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：1 May, 2014
• 年：2014
• 卷：22
• 期：9
• 页码：2662-2670
• 全文大小：2326 K

文摘

A novel compound鈥?鈥?3鈥?4鈥?6鈥?tetra-O-acetyl-尾-d-galactopyranosyl-(1鈫?)-2鈥?3鈥?6鈥?tri-O-acetyl-1-thio-尾-d-glucopyranosyl-(5-nitro-2-pyridyl) sulfoxide鈥攄esignated 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 卤 0.12 渭g/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.