In vitro and in vivo efficacy of Tecovirimat against a recently emerged 2022 Monkeypox virus isolate

The recent emergence of the monkeypox virus (MPXV) in non-endemic countries has been designated a Public Health Emergency of International Concern by the World Health Organization. There are currently no approved treatments for MPXV infection in the United States or Canada. The antiviral drug tecovirimat (commonly called TPOXX), previously approved for smallpox treatment, is currently being deployed for treatment of MPXV infections where available based on previously accrued data. We tested the efficacy of TPOXX both in vitro and in vivo against a clade 2 Canadian 2022 isolate of MPXV isolated during the current outbreak. TPOXX prevented MPXV replication in vitro with an effective concentration in the nanomolar range. In order to evaluate TPOXX efficacy in vivo, we first characterized the CAST/EiJ mouse model with the same 2022 Canadian isolate. Interestingly, unlike previous descriptions of this model, the Canadian isolate was not lethal in CAST/EiJ mice, though it replicated efficiently in the respiratory tract following intranasal infection. Subsequent experiments demonstrated that daily oral TPOXX treatment dramatically reduced viral titers in the tissues one and two weeks following infection. Our data indicate that TPOXX is highly effective against currently circulating MPXV strains and could be an important contributor to curbing the ongoing outbreak.