Fig. 5: Identification of G243-1720-resistant mutations in OPG57 (gene F13L) of MPXV.
From: Development of a replication-defective mpox virus platform for fundamental and therapeutic research
A Specific mutation was identified in the OPG57 gene of rdMPXVΔ96,158. P5 and P10 viruses selected under G243-1720 or DMSO treatment were subjected to next-generation sequencing (NGS) and Sanger sequencing. Three specific mutation sites in the OPG57 gene were identified. B Resistance of the OPG57I372N mutation to G243-1720. HaCat-96,158 cells were pre-treated with G243-1720 (1.5 μM) for 1 h, followed by infection with P5 of rdMPXVΔ96,158 or rdMPXVΔ96,158-OPG57I372N (MOI 0.0005 or 0.005) for 40 h. Cells were fixed and imaged by fluorescence microscopy. Scale bar, 400 μm. C Resistance of OPG57I372N to tecovirimat. HaCat-96,158 cells pre-treated with tecovirimat (0.1 μM) for 1 h were infected with P5 of rdMPXVΔ96,158 or rdMPXVΔ96,158-OPG57I372N (MOI 0.005 or 0.03) for 72 h. Cells were fixed and imaged. Scale bar, 400 μm. D Comparison of resistance mutations in the OPG57 identified for G243-1720, tecovirimat, and IMCBH, another OPG57-targeting small-molecule. Representative images from three independent experiments are shown (B, D).
