Aggarwal Aneel, Kottur Jithesh
Icahn School of Medicine at Mount Sinai.
Res Sq. 2022 Mar 8:rs.3.rs-1370473. doi: 10.21203/rs.3.rs-1370473/v1.
Emergence of SARS-CoV-2 coronavirus has led to millions of deaths globally. We present three high-resolution crystal structures of the SARS-CoV-2 nsp14 N7-methyltransferase core bound to S-adenosylmethionine (SAM; 1.62Å), S-adenosylhomocysteine (SAH; 1.55Å) and Sinefungin (SFG; 1.41Å). We identify features of the methyltransferase core that are crucial for the development of antivirals and show SAH as the best scaffold for the design of antivirals against SARS-CoV-2 and other pathogenic coronaviruses.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的出现已在全球导致数百万人死亡。我们展示了与S-腺苷甲硫氨酸（SAM；1.62Å）、S-腺苷高半胱氨酸（SAH；1.55Å）和杀稻瘟菌素（SFG；1.41Å）结合的SARS-CoV-2 nsp14 N7-甲基转移酶核心的三种高分辨率晶体结构。我们确定了甲基转移酶核心中对抗病毒药物开发至关重要的特征，并表明SAH是设计针对SARS-CoV-2和其他致病性冠状病毒的抗病毒药物的最佳支架。
