Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo nam. 2, 166 10 Prague 6, Czech Republic.
Nucleic Acids Res. 2022 Jan 25;50(2):635-650. doi: 10.1093/nar/gkab1279.
Coronaviral methyltransferases (MTases), nsp10/16 and nsp14, catalyze the last two steps of viral RNA-cap creation that takes place in cytoplasm. This cap is essential for the stability of viral RNA and, most importantly, for the evasion of innate immune system. Non-capped RNA is recognized by innate immunity which leads to its degradation and the activation of antiviral immunity. As a result, both coronaviral MTases are in the center of scientific scrutiny. Recently, X-ray and cryo-EM structures of both enzymes were solved even in complex with other parts of the viral replication complex. High-throughput screening as well as structure-guided inhibitor design have led to the discovery of their potent inhibitors. Here, we critically summarize the tremendous advancement of the coronaviral MTase field since the beginning of COVID pandemic.
冠状病毒甲基转移酶（MTases）、nsp10/16 和 nsp14，催化病毒 RNA 加帽过程中的最后两步，该过程发生在细胞质中。这个帽子对于病毒 RNA 的稳定性至关重要，最重要的是，对于逃避先天免疫系统至关重要。未加帽的 RNA 被先天免疫系统识别，导致其降解和抗病毒免疫的激活。因此，冠状病毒 MTases 都是科学研究的焦点。最近，即使在与病毒复制复合物的其他部分形成复合物的情况下，两种酶的 X 射线和 cryo-EM 结构也被解析。高通量筛选以及基于结构的抑制剂设计导致发现了它们的有效抑制剂。在这里，我们批判性地总结了 COVID 大流行以来冠状病毒 MTase 领域的巨大进展。
