caa a22 4500 475737954 CHVBK 20180406123452.0 cr unu---uuuuu 170329e20001101xx s 000 0 eng 10.1007/s004300000046 doi (NATIONALLICENCE)springer-10.1007/s004300000046 Inhibition of adenovirus DNA polymerase by modified nucleoside triphosphate analogs correlate with their antiviral effects on cellular level [Elektronische Daten] [Renate Mentel, Stefan Kurek, Ursula Wegner, Martin v. Janta-Lipinski, Lutz Gürtler, Eckart Matthes] Adenovirus (Ad) infection results in significant morbidity and mortality in both immunocompetent and immunosuppressed hosts. There is currently no licensed chemotherapy effective in dealing with this virus infection. In this study the anti-adenoviral activity of a group of modified nucleoside analogs was investigated. The most efficient 3-fluorosubstituted nucleoside triphosphate inhibitors of Ad DNA polymerase were 3′-fluorothymidine triphosphate (IC50 0.63 μM), 2′,3′-dideoxy-3′-fluoroguanosine triphosphate (IC50 0.71 μM) and 2′,3′-dideoxy-3′-fluorouridine triphosphate (IC50 2.96 μM). The most efficient 2′,3′-dideoxynucleoside triphosphates were 2′,3′-dideoxycytidine triphosphate (ddCTP; IC50 1.0 μM), 2′,3′-dideoxyadenosine triphosphate (IC50 1.6 μM) and 2′,3′-dideoxythymidine triphosphate (IC50 1.82 μM). Kinetic studies indicate competitive inhibition of adenovirus DNA polymerase by ddCTP. These data confirm results previously obtained at the cellular level using a focus reduction assay involving Ad2-infected FL cells. Whereas the D-enantiomers 3′-fluorothymidine and 2′,3′-dideoxycytidine are potent inhibitors of adenoviral replication, the corresponding L-enantiomers exhibited no inhibitory activity. Springer-Verlag Berlin Heidelberg, 2000 Key words Human adenovirus nationallicence Antiviral activity nationallicence Modified nucleoside analogs nationallicence Polymerase nationallicence L-Enantiomers nationallicence Mentel Renate Friedrich-Loeffler-Institut für Medizinische Mikrobiologie, Ernst-Moritz-Arndt-Universität Greifswald, Martin-Luther-Strasse 6, 17487 Greifswald, Germany Tel.: +49-3834-865580; Fax: +49-3834-865561, DE aut Kurek Stefan Friedrich-Loeffler-Institut für Medizinische Mikrobiologie, Ernst-Moritz-Arndt-Universität Greifswald, Martin-Luther-Strasse 6, 17487 Greifswald, Germany Tel.: +49-3834-865580; Fax: +49-3834-865561, DE aut Wegner Ursula Friedrich-Loeffler-Institut für Medizinische Mikrobiologie, Ernst-Moritz-Arndt-Universität Greifswald, Martin-Luther-Strasse 6, 17487 Greifswald, Germany Tel.: +49-3834-865580; Fax: +49-3834-865561, DE aut v. Janta-Lipinski Martin Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, 13092 Berlin, Germany, DE aut Gürtler Lutz Friedrich-Loeffler-Institut für Medizinische Mikrobiologie, Ernst-Moritz-Arndt-Universität Greifswald, Martin-Luther-Strasse 6, 17487 Greifswald, Germany Tel.: +49-3834-865580; Fax: +49-3834-865561, DE aut Matthes Eckart Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, 13092 Berlin, Germany, DE aut https://doi.org/10.1007/s004300000046 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s004300000046 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mentel Renate Friedrich-Loeffler-Institut für Medizinische Mikrobiologie, Ernst-Moritz-Arndt-Universität Greifswald, Martin-Luther-Strasse 6, 17487 Greifswald, Germany Tel.: +49-3834-865580; Fax: +49-3834-865561, DE aut NATIONALLICENCE 700 1- Kurek Stefan Friedrich-Loeffler-Institut für Medizinische Mikrobiologie, Ernst-Moritz-Arndt-Universität Greifswald, Martin-Luther-Strasse 6, 17487 Greifswald, Germany Tel.: +49-3834-865580; Fax: +49-3834-865561, DE aut NATIONALLICENCE 700 1- Wegner Ursula Friedrich-Loeffler-Institut für Medizinische Mikrobiologie, Ernst-Moritz-Arndt-Universität Greifswald, Martin-Luther-Strasse 6, 17487 Greifswald, Germany Tel.: +49-3834-865580; Fax: +49-3834-865561, DE aut NATIONALLICENCE 700 1- v. Janta-Lipinski Martin Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, 13092 Berlin, Germany, DE aut NATIONALLICENCE 700 1- Gürtler Lutz Friedrich-Loeffler-Institut für Medizinische Mikrobiologie, Ernst-Moritz-Arndt-Universität Greifswald, Martin-Luther-Strasse 6, 17487 Greifswald, Germany Tel.: +49-3834-865580; Fax: +49-3834-865561, DE aut NATIONALLICENCE 700 1- Matthes Eckart Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, 13092 Berlin, Germany, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer