{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:20:59Z","timestamp":1791980459760,"version":"4.4.0"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Tick-borne encephalitis virus (TBEV) is a leading cause of human neuroinfections in Europe and Northeast Asia. There are no antiviral therapies for treating TBEV infection. A series of nucleoside analogues was tested for the ability to inhibit the replication of TBEV in porcine kidney cells and human neuroblastoma cells. The interactions of three nucleoside analogues with viral polymerase were simulated using advanced computational methods. The nucleoside analogues 7-deaza-2\u2032-\n            <jats:italic>C<\/jats:italic>\n            -methyladenosine (7-deaza-2\u2032-CMA), 2\u2032-\n            <jats:italic>C<\/jats:italic>\n            -methyladenosine (2\u2032-CMA), and 2\u2032-C-methylcytidine (2\u2032-CMC) inhibited TBEV replication. These compounds showed dose-dependent inhibition of TBEV-induced cytopathic effects, TBEV replication (50% effective concentrations [EC\n            <jats:sub>50<\/jats:sub>\n            ]of 5.1 \u00b1 0.4 \u03bcM for 7-deaza-2\u2032-CMA, 7.1 \u00b1 1.2 \u03bcM for 2\u2032-CMA, and 14.2 \u00b1 1.9 \u03bcM for 2\u2032-CMC) and viral antigen production. Notably, 2\u2032-CMC was relatively cytotoxic to porcine kidney cells (50% cytotoxic concentration [CC\n            <jats:sub>50<\/jats:sub>\n            ] of \u223c50 \u03bcM). The anti-TBEV effect of 2\u2032-CMA in cell culture diminished gradually after day 3 posttreatment. 7-Deaza-2\u2032-CMA showed no detectable cellular toxicity (CC\n            <jats:sub>50<\/jats:sub>\n            &gt; 50 \u03bcM), and the antiviral effect in culture was stable for &gt;6 days posttreatment. Computational molecular analyses revealed that compared to the other two compounds, 7-deaza-2\u2032-CMA formed a large cluster near the active site of the TBEV polymerase. High antiviral activity and low cytotoxicity suggest that 7-deaza-2\u2032-CMA is a promising candidate for further investigation as a potential therapeutic agent in treating TBEV infection.\n          <\/jats:p>","DOI":"10.1128\/aac.00807-15","type":"journal-article","created":{"date-parts":[[2015,6,30]],"date-time":"2015-06-30T02:44:58Z","timestamp":1435632298000},"page":"5483-5493","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":97,"title":["Nucleoside Inhibitors of Tick-Borne Encephalitis Virus"],"prefix":"10.1128","volume":"59","author":[{"given":"Lud\u011bk","family":"Eyer","sequence":"first","affiliation":[{"name":"Department of Virology, Veterinary Research Institute, Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Vald\u00e9s","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, \u010cesk\u00e9 Bud\u011bjovice, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor A.","family":"Gil","sequence":"additional","affiliation":[{"name":"Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radim","family":"Nencka","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"H\u0159ebabeck\u00fd","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"\u0160\u00e1la","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u0159\u00ed","family":"Sal\u00e1t","sequence":"additional","affiliation":[{"name":"Department of Virology, Veterinary Research Institute, Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u0159\u00ed","family":"\u010cern\u00fd","sequence":"additional","affiliation":[{"name":"Department of Virology, Veterinary Research Institute, Brno, Czech Republic"},{"name":"Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, \u010cesk\u00e9 Bud\u011bjovice, Czech Republic"},{"name":"Faculty of Science, University of South Bohemia, \u010cesk\u00e9 Bud\u011bjovice, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Palus","sequence":"additional","affiliation":[{"name":"Department of Virology, Veterinary Research Institute, Brno, Czech Republic"},{"name":"Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, \u010cesk\u00e9 Bud\u011bjovice, Czech Republic"},{"name":"Faculty of Science, University of South Bohemia, \u010cesk\u00e9 Bud\u011bjovice, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"De Clercq","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"R\u016f\u017eek","sequence":"additional","affiliation":[{"name":"Department of Virology, Veterinary Research Institute, Brno, Czech Republic"},{"name":"Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, \u010cesk\u00e9 Bud\u011bjovice, Czech Republic"},{"name":"Faculty of Science, University of South Bohemia, \u010cesk\u00e9 Bud\u011bjovice, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"89","volume-title":"Flavivirus encephalitis","author":"Baier A","year":"2011","unstructured":"Baier A. 2011. 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