{"id":2114,"date":"2026-05-07T17:30:31","date_gmt":"2026-05-07T15:30:31","guid":{"rendered":"https:\/\/sites.unica.it\/pe2026\/?p=2114"},"modified":"2026-05-08T17:54:11","modified_gmt":"2026-05-08T15:54:11","slug":"gyde-bandowski","status":"publish","type":"post","link":"https:\/\/sites.unica.it\/pe2026\/2026\/05\/07\/gyde-bandowski\/","title":{"rendered":"Gyde Bandowski"},"content":{"rendered":"\n
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PC3 – Gyde Bandowski<\/strong><\/p>\n\n\n\n

Department of Chemistry, Organic Chemistry, Faculty of Sciences, University of Hamburg, Hamburg, Germany<\/p>\n\n\n\n

gyde.bandowski@uni-hamburg.de<\/strong><\/p>\n<\/div><\/div>\n\n\n\n

Synthesis of \u03b3<\/em>-monoalkylated Triphosphate Analogues to inhibit SARS-CoV-2 Replication-Transcription Complex<\/strong><\/strong><\/strong><\/td><\/tr>
Gyde Bandowski1<\/sup>, Paolo Malune2<\/sup>, Francesca Esposito2<\/sup>, Antonio Lupia2<\/sup>, Simona Distinto2<\/sup>, Elias Maccioni2<\/sup>, Xiao\u00a0Jia1,3<\/sup>, Giuliano Kullik1<\/sup>, Enzo Tramontano2, <\/sup>Chris Meier1,4<\/sup><\/em>

1<\/sup><\/em> Department of Chemistry, Organic Chemistry, Faculty of Sciences, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany;
2<\/sup> Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Cagliari, 09124, Italy;
3<\/sup> State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
4<\/sup> Centre for Structural Systems Biology (CSSB), Hamburg, DESY Campus, Notkestrasse 85, 22607 Hamburg, Germany
<\/td><\/tr>
Abstract<\/strong>
Acyclic nucleoside phosphonates, such as (S<\/em>)-HPMPC, have shown significant antiviral activity against a range of viruses [1]. Based on the structure of (S<\/em>)-HPMPC, we synthesised a series of \u03b3<\/em>\u2011monoalkylated nucleoside phosphonate diphosphates and their prodrugs with different nucleobases and alkyl chain lengths, by applying the H<\/em>\u2011phosphonate route for the synthesis of TriPPP<\/em>ro-compounds. This way, the enzymatic phosphorylation to the biological active triphosphate analogue is bypassed [2]. The \u03b3<\/em>\u2011monoalkylated compounds were found to inhibit the viral RNA-dependent RNA polymerase (RdRp) complex of SARS-CoV\u20112 with a novel unusual mechanism of action. Enzymatic PAGE-based assays of the minimal replication-transcription complex (RTC) of SARS\u2011CoV-2 showed complete loss of enzymatic function of the RdRp with no incorporation of the nucleotide analogues and no competition with natural nucleoside triphosphates. IC50<\/sub> values in the low micromolar range were determined in dependence on the length of the \u03b3<\/em>-alkyl group. Using multiple techniques, we were able to identify the mechanism of action in the compound-induced dissociation of the nsp7 cofactor from the nsp12 subunit. Molecular docking confirmed the binding site, identifying putative amino acid residues relevant for compound interaction.\u00a0To further investigate of the novel mechanism of action, other nucleotide analogues were synthesised, to determine which structural motifs of the compounds are involved in binding and thus are responsible for their inhibitory action. IC50 <\/sub>values for \u03b3<\/em>-monoalkylated nucleotide analogues with different nucleoside cores and varying numbers of phosphate moieties were evaluated.

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References  <\/strong>
[1] De Clercq, E.; Hol\u00fd, A. Acylic nucleoside phosphonates: a key class of antiviral drugs. Nat. Rev. Drug Discov.<\/em> 2005<\/strong>, 4<\/em>, 928-940.
[2] Gollnest, T.; de Oliveira, T. D.; Schols, D.; Balzarini, J.; Meier, C. Lipophilic prodrugs of nucleoside triphosphates as biochemical probes and potential antivirals. Nat. Commun.<\/em> 2015<\/strong>, 6<\/em>, 8716.<\/td><\/tr><\/tbody><\/table><\/div><\/figure>\n","protected":false},"excerpt":{"rendered":"

PC3 – Gyde Bandowski Department of Chemistry, Organic Chemistry, Faculty of Sciences, University of Hamburg, Hamburg, Germany gyde.bandowski@uni-hamburg.de Synthesis of \u03b3-monoalkylated Triphosphate Analogues to inhibit SARS-CoV-2 Replication-Transcription Complex Gyde Bandowski1, Paolo Malune2, Francesca Esposito2, Antonio Lupia2, […]<\/p>\n","protected":false},"author":10371,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-2114","post","type-post","status-publish","format-standard","hentry","category-senza-categoria"],"_links":{"self":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2114","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/users\/10371"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/comments?post=2114"}],"version-history":[{"count":6,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2114\/revisions"}],"predecessor-version":[{"id":2366,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2114\/revisions\/2366"}],"wp:attachment":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/media?parent=2114"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/categories?post=2114"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/tags?post=2114"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}