0573932 - ÚOCHB 2024 RIV DE eng J - Journal Article
Duchoslav, Vojtěch - Bouřa, Evžen
Structure of monkeypox virus poxin: implications for drug design.
Archives of Virology. Roč. 168, č. 7 (2023), č. článku 192. ISSN 0304-8608. E-ISSN 1432-8798
R&D Projects: GA MŠMT(CZ) LX22NPO5103
Grant - others:AV ČR(CZ) StrategieAV21/25
Program: StrategieAV
Research Infrastructure: CIISB III - 90242
Institutional support: RVO:61388963
Keywords : virus * poxin * nuclease * crystal structure
OECD category: Virology
Impact factor: 2.7, year: 2022
Method of publishing: Open access
https://doi.org/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.
Permanent Link: https://hdl.handle.net/11104/0344320


Research data: PDB