Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i, Flemingovo nám. 2, 166 10, Prague 6, Czech Republic.
Arch Virol. 2023 Jun 28;168(7):192. doi: 10.1007/s00705-023-05824-4.
Monkeypox, or mpox, is a disease that has recently resurfaced and spread across the globe. Despite the availability of an FDA-approved vaccine (JYNNEOS) and an effective drug (tecovirimat), concerns remain over the possible recurrence of a viral pandemic. Like any other virus, mpox virus must overcome the immune system to replicate. Viruses have evolved various strategies to overcome both innate and adaptive immunity. Poxviruses possess an unusual nuclease, poxin, which cleaves 2'-3'-cGAMP, a cyclic dinucleotide, which is an important second messenger in the cGAS-STING signaling pathway. Here, we present the crystal structure of mpox poxin. The structure reveals a conserved, predominantly β-sheet fold and highlights the high conservation of the cGAMP binding site and of the catalytic residues His17, Tyr138, and Lys142. This research suggests that poxin inhibitors could be effective against multiple poxviruses.
猴痘，或称为 mpox，是一种最近重新出现并在全球范围内传播的疾病。尽管有 FDA 批准的疫苗（JYNNEOS）和有效的药物（tecovirimat），但人们仍然担心病毒大流行可能会再次发生。与任何其他病毒一样，mpox 病毒必须克服免疫系统才能复制。病毒已经进化出各种策略来克服先天和适应性免疫。痘病毒具有一种不寻常的核酸酶，即 poxin，它可以切割 2'-3'-cGAMP，一种环状二核苷酸，它是 cGAS-STING 信号通路中的重要第二信使。在这里，我们展示了 mpox poxin 的晶体结构。该结构揭示了一个保守的、主要是 β-折叠结构，并突出了 cGAMP 结合位点和催化残基 His17、Tyr138 和 Lys142 的高度保守性。这项研究表明，poxin 抑制剂可能对多种痘病毒有效。
