Tecovirimat-resistant mutations generated by in vitro cell culture identified targets at F13L amino acid residues conserved among several poxviruses . Some of those resistant mutations were located toward its carboxyterminal domain . Most recently, some of those earlier reported poxvirus mutations were confirmed while other were reported for the first time in MPXV patients resistant to Tecovirimat-treatment (Table and Figure ). These and other recent results suggested that in ~ 5 % of the MPXV patients, Tecovirimat resistant mutations arised during treatment, specially in immunocompromised patients where those percentages could be higher . Although preliminary use of Tecovirimat was recommended for the most recent MPXV clade I African and global infections appearing during 2024 , early results from Africa clinical trial showed that Tecovirimat was not better than placebo against MPXV clade I 40 . Therefore, alternative drugs are needed. Despite many efforts , no other potent inhibitors targeting Tecovirimat-resistant poxviruses have been yet reported .