التفاصيل البيبلوغرافية
| العنوان: |
The Structure-Based Design of SARS-CoV‑2 nsp14 Methyltransferase Ligands Yields Nanomolar Inhibitors |
| المؤلفون: |
Tomáš Otava (11002064), Michal Šála (1398271), Fengling Li (176389), Jindřich Fanfrlík (1265010), Kanchan Devkota (1822468), Sumera Perveen (9974693), Irene Chau (2276365), Paknoosh Pakarian (171283), Pavel Hobza (1279320), Masoud Vedadi (210076), Evzen Boura (302259), Radim Nencka (808341) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biochemistry, Microbiology, Molecular Biology, Pharmacology, Infectious Diseases, Plant Biology, Virology, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, methyl group, homology model, SARS-CoV nsp 14, crystal structure, SARS-CoV -2 nsp 14, SARS-CoV -2 methyltransferases, SAM, guanosine triphosphate moiety, docking studies, Structure-Based Design, adenine nucleobase, MTase catalyzes, position 7, novel SAH derivatives, 7- deaza analogues, inhibitor, RNA |
| الوصف: |
In this study, we have focused on the structure-based design of the inhibitors of one of the two SARS-CoV-2 methyltransferases (MTases), nsp14. This MTase catalyzes the transfer of the methyl group from S -adenosyl-l-methionine (SAM) to cap the guanosine triphosphate moiety of the newly synthesized viral RNA, yielding the methylated capped RNA and S -adenosyl-l-homocysteine (SAH). As the crystal structure of SARS-CoV-2 nsp14 is unknown, we have taken advantage of its high homology to SARS-CoV nsp14 and prepared its homology model, which has allowed us to identify novel SAH derivatives modified at the adenine nucleobase as inhibitors of this important viral target. We have synthesized and tested the designed compounds in vitro and shown that these derivatives exert unprecedented inhibitory activity against this crucial enzyme. The docking studies nicely explain the contribution of an aromatic part attached by a linker to the position 7 of the 7-deaza analogues of SAH. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/journal_contribution/The_Structure-Based_Design_of_SARS-CoV_2_nsp14_Methyltransferase_Ligands_Yields_Nanomolar_Inhibitors/14818016 |
| DOI: |
10.1021/acsinfecdis.1c00131.s001 |
| الاتاحة: |
https://doi.org/10.1021/acsinfecdis.1c00131.s001 |
| Rights: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.BCA0B113 |
| قاعدة البيانات: |
BASE |