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Publication Abstract from PubMed

In July 2022, the World Health Organization announced monkeypox as a public health emergency of international concern (PHEIC), and over 85,000 global cases have been reported currently. However, preventive and therapeutic treatments for the monkeypox virus (MPXV) remain limited. MPXV mRNA cap N7 methyltransferase (MTase) is composed of two subunits (E1 C-terminal domain (E1(CTD)) and E12) which are essential for the replication of MPXV. Here, we solved a 2.16 A crystal structure of E12. We also docked the D1(CTD) of the vaccinia virus (VACV) corresponding to the E1(CTD) in MPXV with E12 and found critical residues at their interface. These residues were further used for drug screening. After virtual screening, the top 347 compounds were screened out and a list of top 20 potential MPXV E12 inhibitors were discovered, including Rutin, Quercitrin, Epigallocatechin, Rosuvastatin, 5-hydroxy-L-Tryptophan, and Deferasirox, etc., which were potential E12 inhibitors. Taking the advantage of the previously unrecognized special structure of MPXV MTase composing of E1(CTD) and E12 heterodimer, we screened for inhibitors targeting MTase for the first time based on the interface between the heterodimer of MPXV MTase. Our study may provide insights into the development of anti-MPXV drugs.

Crystal structure of mRNA cap (guanine-N7) methyltransferase E12 subunit from monkeypox virus and discovery of its inhibitors.,Wang DP, Zhao R, Wang HF, Wang MY, Hu WS, Lin MM, Shu W, Sun YJ, Cao JM, Cui W, Zhou X Int J Biol Macromol. 2023 Dec 31;253(Pt 8):127565. doi: , 10.1016/j.ijbiomac.2023.127565. Epub 2023 Oct 20. PMID:37866584^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.