Academic Journal
The Movie Group.
| العنوان: | The Movie Group. |
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| المؤلفون: | Bach Tran Nguyen, Aurélien Marc, Clara Suñer, Michael Marks, Maria Ubals, Águeda Hernández-Rodríguez, María Ángeles Melendez, Dennis E. Hruby, Andrew T. Russo, France Mentré, Oriol Mitjà, Douglas W. Grosenbach, Jérémie Guedj |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Medicine, Microbiology, Molecular Biology, Pharmacology, Biotechnology, Evolutionary Biology, Immunology, Cancer, Mental Health, Infectious Diseases, Virology, Computational Biology, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, 54 untreated patients, estimated mpox within, drug steady state, positive viral culture, pharmacological model developed, div >< p, viral dynamic model, characterize mpox kinetics, viral kinetics, mpox infection, drug administration, viral peak, mpox clearance, viral clearance, unique set, symptom onset |
| الوصف: | 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 within-host basic reproduction number, R 0 , 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 about 6 days. Immediate postexposure prophylaxis could not only reduce time to clearance but also lower peak viral load by more than 1.0 log 10 copies/mL and shorten the duration of positive viral culture by about 7 to 10 days. These findings support the early administration of tecovirimat against mpox infection, ideally starting from the infection day as a postexposure prophylaxis. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | https://figshare.com/articles/journal_contribution/The_Movie_Group_/24887440 |
| DOI: | 10.1371/journal.pbio.3002249.s015 |
| الاتاحة: | https://doi.org/10.1371/journal.pbio.3002249.s015 https://figshare.com/articles/journal_contribution/The_Movie_Group_/24887440 |
| Rights: | CC BY 4.0 |
| رقم الانضمام: | edsbas.5E1B1939 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.pbio.3002249.s015 |
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