生物
机制(生物学)
核苷酸
病毒学
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)
GTP'
2019年冠状病毒病(COVID-19)
RNA依赖性RNA聚合酶
核糖核酸
RNA聚合酶
2019-20冠状病毒爆发
作用机理
聚合酶
生物化学
细胞生物学
立体化学
DNA
遗传学
酶
化学
基因
体外
传染病(医学专业)
爆发
病理
认识论
疾病
哲学
医学
作者
Liming Yan,Yucen Huang,Ji Ge,Zhenyu Liu,Pengchi Lu,Bo Huang,Shan Gao,Junbo Wang,Liping Tan,Sihan Ye,Fengxi Yu,Weiqi Lan,Shiya Xu,Feng Zhou,Lei Shi,Luke W. Guddat,Yan Gao,Zihe Rao,Zhiyong Lou
出处
期刊:Cell
[Elsevier]
日期:2022-10-01
卷期号:185 (23): 4347-4360.e17
被引量:2
标识
DOI:10.1016/j.cell.2022.09.037
摘要
Decoration of cap on viral RNA plays essential roles in SARS-CoV-2 proliferation. Here, we report a mechanism for SARS-CoV-2 RNA capping and document structural details at atomic resolution. The NiRAN domain in polymerase catalyzes the covalent link of RNA 5' end to the first residue of nsp9 (termed as RNAylation), thus being an intermediate to form cap core (GpppA) with GTP catalyzed again by NiRAN. We also reveal that triphosphorylated nucleotide analog inhibitors can be bonded to nsp9 and fit into a previously unknown "Nuc-pocket" in NiRAN, thus inhibiting nsp9 RNAylation and formation of GpppA. S-loop (residues 50-KTN-52) in NiRAN presents a remarkable conformational shift observed in RTC bound with sofosbuvir monophosphate, reasoning an "induce-and-lock" mechanism to design inhibitors. These findings not only improve the understanding of SARS-CoV-2 RNA capping and the mode of action of NAIs but also provide a strategy to design antiviral drugs.
科研通智能强力驱动
Strongly Powered by AbleSci AI