6-氯嘌呤异恶唑啉-碳环单磷酸核苷酸对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的RNA依赖性RNA聚合酶的抑制作用

Inhibition of the RNA-Dependent RNA-Polymerase from SARS-CoV-2 by 6-Chloropurine Isoxazoline-Carbocyclic Monophosphate Nucleotides.

作者信息

Leusciatti Marco, Macchi Beatrice, Marino-Merlo Francesca, Mastino Antonio, Morra Giulia, Quadrelli Paolo

机构信息

Department of Chemistry, University of Pavia, Viale Taramelli 12, 27100 Pavia,Italy.

Department of Chemical Science and Technology, University of Rome Tor Vergata, Via della ricerca scientifica 1, 00133 Roma, Italy.

出版信息

ACS Omega. 2023 Sep 20;8(39):36311-36320. doi: 10.1021/acsomega.3c04918. eCollection 2023 Oct 3.

Isoxazoline-carbocyclic monophosphate nucleotides were designed and synthesized through the chemistry of nitrosocarbonyl intermediates and stable anthracenenitrile oxide. Docking and molecular dynamics studies were first conducted for determining the best candidate for polymerase SARS-CoV-2 inhibition. The setup phosphorylation protocol afforded the nucleotides available for the biological tests. Preliminary inhibition and cytotoxicity assays were then performed, and the results showed a moderate activity of the nucleotides accompanied by cytotoxicity.