Ahmed-Belkacem, Rostom; Hausdorff, Marcel; Delpal, Adrien; Sutto-Ortiz, Priscila; Colmant, Agathe M. G.; Touret, Franck; Ogando, Natacha S.; Snijder, Eric J.; Canard, Bruno; Coutard, Bruno; Vasseur, Jean-Jacques; Decroly, Etienne; Debart, Francoise published the artcile< Potent Inhibition of SARS-CoV-2 nsp14 N7-Methyltransferase by Sulfonamide-Based Bisubstrate Analogues>, Category: chlorides-buliding-blocks, the main research area is SARSCoV2 nsp14 methyltransferase inhibitor synthesis COVID19 sulfonamide bisubstrate analog.
Enzymes involved in RNA capping of SARS-CoV-2 are essential for the stability of viral RNA, translation of mRNAs, and virus evasion from innate immunity, making them attractive targets for antiviral agents. In this work, we focused on the design and synthesis of nucleoside-derived inhibitors against the SARS-CoV-2 nsp14 (N7-guanine)-methyltransferase (N7-MTase) that catalyzes the transfer of the Me group from the S-adenosyl-L-methionine (SAM) cofactor to the N7-guanosine cap. Seven compounds out of 39 SAM analogs showed remarkable double-digit nanomolar inhibitory activity against the N7-MTase nsp14. Mol. docking supported the structure-activity relationships of these inhibitors and a bisubstrate-based mechanism of action. The three most potent inhibitors significantly stabilized nsp14 (ΔTm ≈ 11°C), and the best inhibitor demonstrated high selectivity for nsp14 over human RNA N7-MTase.
Journal of Medicinal Chemistry published new progress about Anticoronaviral agents. 42413-03-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O2S, Category: chlorides-buliding-blocks.
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