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However, this metabolic activation is rate\u2010limiting and inefficient. We here report the chemical synthesis and evaluation of three series of T\u20101105\u2010ribonucleoside (T\u20101106)\u2010Di\n                    <jats:italic>PP<\/jats:italic>\n                    ro\u2010 and Tri\n                    <jats:italic>PPP<\/jats:italic>\n                    ro\u2010nucleotide prodrugs to allow their cellular uptake. Their efficient release of the T\u20101106\u2010diphosphate and triphosphate forms was demonstrated upon incubation in PBS, pig liver esterase, extract of human T\u2010lymphoblast CEM\/0 cells and human plasma. This validates the successful hydrolysis and delivery of the corresponding nucleotides, via chemical or enzyme\u2010triggered mechanisms. Interestingly, several T\u20101106\u2010Di\n                    <jats:italic>PP<\/jats:italic>\n                    ro\u2010prodrugs, for example, compound\n                    <jats:bold>24h<\/jats:bold>\n                    , and Tri\n                    <jats:italic>PPP<\/jats:italic>\n                    ro\u2010prodrugs proved superior to the parent T\u20101106 nucleoside, in inhibiting influenza A and influenza B replication in MDCK cells, and of human coronavirus OC43 in HEL299 cells. This validates the utility of our pronucleotide strategy to overcome the inefficient activation of T\u20101106 and increase the antiviral efficacy against influenza and coronaviruses.\n                  <\/jats:p>","DOI":"10.1002\/chem.71181","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T08:15:52Z","timestamp":1779869752000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Membrane\u2010Permeable Nucleoside T\u20101106 Diphosphate and Triphosphate Analogues as Antiviral Pronucleotides"],"prefix":"10.1002","volume":"32","author":[{"given":"Chris","family":"Meier","sequence":"first","affiliation":[{"name":"Organic Chemistry Department of Chemistry Faculty of Mathematics Informatics and Natural Sciences Universit\u00e4t Hamburg  Hamburg Germany"},{"name":"Centre for Structural Systems Biology (CSSB) Hamburg DESY Campus  Hamburg 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