核糖核酸
甲基转移酶
生物
病毒学
转移酶
RNA病毒
DNA
病毒
猴痘
酶
遗传学
生物化学
基因
重组DNA
甲基化
牛痘
作者
Jan Šilhán,Martin Klíma,Tomáš Otava,Petr Skvara,Dominika Chalupská,Karel Chalupský,Jan Kozic,Radim Nencka,Evžen Bouřa
标识
DOI:10.1038/s41467-023-38019-1
摘要
Monkeypox is a disease with pandemic potential. It is caused by the monkeypox virus (MPXV), a double-stranded DNA virus from the Poxviridae family, that replicates in the cytoplasm and must encode for its own RNA processing machinery including the capping machinery. Here, we present crystal structures of its 2'-O-RNA methyltransferase (MTase) VP39 in complex with the pan-MTase inhibitor sinefungin and a series of inhibitors that were discovered based on it. A comparison of this 2'-O-RNA MTase with enzymes from unrelated single-stranded RNA viruses (SARS-CoV-2 and Zika) reveals a conserved sinefungin binding mode, implicating that a single inhibitor could be used against unrelated viral families. Indeed, several of our inhibitors such as TO507 also inhibit the coronaviral nsp14 MTase.
科研通智能强力驱动
Strongly Powered by AbleSci AI