Inhibitors of mpox VP39 2′-O methyltransferase efficiently inhibit the monkeypox virus

0576080 - ÚOCHB 2024 RIV NL eng J - Journal Article
Zgarbová, Michala - Otava, Tomáš - Šilhán, Jan - Nencka, Radim - Weber, Jan - Bouřa, Evžen
Inhibitors of mpox VP39 2′-O methyltransferase efficiently inhibit the monkeypox virus.
Antiviral Research. Roč. 218, October (2023), č. článku 105714. ISSN 0166-3542. E-ISSN 1872-9096
R&D Projects: GA MŠMT(CZ) LX22NPO5103
Institutional support: RVO:61388963
Keywords : structural basis
OECD category: Virology
Impact factor: 7.6, year: 2022
Method of publishing: Open access
https://doi.org/10.1016/j.antiviral.2023.105714

The RNA 2′-O methyltransferase (MTase) VP39 of the monkeypox virus (MpxV) participates in RNA capping within poxviruses. Sub-micromolar inhibitors targeting this enzyme were already reported. However, these 7-deaza analogs of S-adenosyl methionine (SAH) had not been tested in cellular assays until now. In this study, we employed plaque assays and cytopathic effect-based assays to evaluate the effectiveness of these compounds. All tested compounds demonstrated antiviral activity against MpxV, with EC50 values ranging from 0.06 to 2.7 μM. Nevertheless, some of these compounds also exhibited cytotoxicity in HeLa cells, while others showed no toxicity. Notably, the non-toxic compounds featured a large aromatic substituent at the 7-deaza position, whereas the toxic compounds had a small substituent at the same position. These findings suggest that VP39 represents a bona fide target for the development of antiviral drugs against MpxV.
Permanent Link: https://hdl.handle.net/11104/0345703