Crystal structure of mRNA cap (guanine-N7) methyltransferase E12 subunit from monkeypox virus and discovery of its inhibitors

In July 2022, the World Health Organization announced monkeypox as a public health emergency of international concern (PHEIC), over 85,000 global cases have been reported currently. However, preventive and therapeutic treatments are very limited. The monkeypox virus (MPXV) E12, an mRNA capping enzyme small subunit, is essential for the methyltransferase activity of RNA capping enzymes of MPXV. Here, we solved a 2.16 Å crystal structure of E12. We also docked the D1 subunit c-terminal domain (D1 CTD ) of vaccinia virus (VACV) with E12 to analyze the critical residues of interface between them. These residues are used for drug screening. The top six compounds are Rutin, Quercitrin, Epigallocatechin, Rosuvastatin, 5-hydroxy-L-Tryptophan, and Deferasirox. These findings may provide insights into the development of anti-MPXV drugs.