Early administration of tecovirimat shortens the time to mpox clearance in a model of human infection

by Bach Tran Nguyen, Aur élien Marc, Clara Suñer, Michael Marks, Maria Ubals, Águeda Hernández-Rodríguez, María Ángeles Melendez, The Movie Group , Dennis E. Hruby, Andrew T. Russo, France Mentré, Oriol Mitjà, Douglas W. Grosenbach, Jérémie Guedj Despite use of tecovirimat since the beginning of the 2022 outbreak, few data have been published on its antiviral effect in humans. We here predict tecovirimat efficacy using a unique set of data in nonhuman primates (NHPs) and humans. We analyzed tecovirimat antiviral activity on viral kinetics in NHP to characterize its concentration –effect relationship in vivo. Next, we used a pharmacological model developed in healthy volunteers to project its antiviral efficacy in humans. Finally, a viral dynamic model was applied to characterize mpox kinetics in skin lesions from 54 untreated patients, and we used this modeling framework to predict the impact of tecovirimat on viral clearance in skin lesions. At human-recommended doses, tecovirimat could inhibit viral replication from infected cells by more than 90% after 3 to 5 days of drug administration and achieved over 97% efficacy at drug steady state. With an estimated mpox w ithin-host basic reproduction number, R0, equal to 5.6, tecovirimat could therefore shorten the time to viral clearance if given before viral peak. We predicted that initiating treatment at symptom onset, which on average occurred 2 days before viral peak, could reduce the time to viral clearance by ...
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research