Monkeypox Virus Is Inhibited by Nucleoside Analogues Including the Acyclic Phosphonates Adefovir and Tenofovir In Vitro.

Mpox, caused by the orthopoxvirus monkeypox virus (MPXV), has garnered worldwide attention during a global outbreak in 2022 and in an ongoing outbreak in Central Africa. Because of drug resistance and toxicity risks with current antiviral treatments, there is still a need for additional antivirals to treat mpox and other orthopoxvirus diseases. We developed in vitro screening assays using recombinant strains of vaccinia virus and MPXV to measure the antiviral potency of compounds, finding that adefovir dipivoxil and tenofovir alafenamide had potent anti-orthopoxvirus activity and low toxicity. These data reinforce interest in repurposing nucleoside analogues as antivirals to treat poxvirus infections and provide a basis for high throughput screening and mechanistic and antiviral resistance studies.