Among all single F13L mutations, those showing Tecovirimatresistance phenotypes with the highest EC50 > 500 µM were included into several mutants designed here (Figure , red solid spheres ). These high EC50 mutants suggest that several single mutations might be necessary to confer the highest Tecovirimat-resistances. Compared to the MPXV reference strain clade IIa (2003) with a susceptibility of EC50 = 17.5 nM Tecovirimat (published data from Table of Smith et al ), the resistant mutations showing higher EC50, suggested to the authors of those studies that they were Tecovirimat-treatment-dependent, specially those emerging from immuno-compromised patients.