Discovery and structural characterization of monkeypox virus methyltransferase VP39 inhibitors reveal similarities to SARS-CoV-2 nsp14 methyltransferase

0571446 - ÚOCHB 2024 RIV US eng J - Článek v odborném periodiku
Šilhán, Jan - Klíma, Martin - Otava, Tomáš - Škvára, Petr - Chalupská, Dominika - Chalupský, Karel - Kozic, Ján - Nencka, Radim - Bouřa, Evžen
Discovery and structural characterization of monkeypox virus methyltransferase VP39 inhibitors reveal similarities to SARS-CoV-2 nsp14 methyltransferase.
Nature Communications. Roč. 14, April (2023), č. článku 2259. E-ISSN 2041-1723
Grant CEP: GA MŠMT(CZ) LX22NPO5103
Institucionální podpora: RVO:61388963
Klíčová slova: messenger RNA * recognition * binding
Obor OECD: Virology
Impakt faktor: 16.6, rok: 2022
Způsob publikování: Open access
https://doi.org/10.1038/s41467-023-38019-1

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.
Trvalý link: https://hdl.handle.net/11104/0342665