Rasmussen, H.B.; Hansen, P.R. Molnupiravir Revisited—Critical Assessment of Studies in Animal Models of COVID-19. Viruses2023, 15, 2151.
Rasmussen, H.B.; Hansen, P.R. Molnupiravir Revisited—Critical Assessment of Studies in Animal Models of COVID-19. Viruses 2023, 15, 2151.
Rasmussen, H.B.; Hansen, P.R. Molnupiravir Revisited—Critical Assessment of Studies in Animal Models of COVID-19. Viruses2023, 15, 2151.
Rasmussen, H.B.; Hansen, P.R. Molnupiravir Revisited—Critical Assessment of Studies in Animal Models of COVID-19. Viruses 2023, 15, 2151.
Abstract
Molnupiravir, a prodrug known for its broad antiviral activity, demonstrated efficacy in animal models of Covid-19, prompting clinical trials where initial results indicated a significant effect against the disease. However, subsequent clinical studies did not confirm these findings, leading to the rejection of molnupiravir for permanent market authorization in many countries. This report critically assessed 19 studies published in 17 reports that investigated the efficacy of molnupiravir in animal models of Covid-19 with the purpose of determining how well the design of these models informed human studies. We found that the administered doses of molnupiravir in most studies involving animal Covid-19 models were disproportionately higher than the dose rec-ommended for human use. Specifically, when adjusted for body surface area, half of the doses of molnupiravir used in the animal studies were more than twice as high as the human dose. Addi-tionally, the drug was frequently given prophylactically or shortly after SARS-CoV-2 inoculation in these models, in contrast to clinical trials where such timing is not consistently achieved. Furthermore, the recommended five-day treatment duration for humans was exceeded in several animal studies. Collectively, we suggest that these design elements in the reported animal studies contributed to a bias favoring molnupiravir, and thus inflated expectations for its efficacy against Covid-19. Addressing these elements may offer avenues to enhance the clinical efficacy of mol-nupiravir for treatment of Covid-19 that include dose increment, early treatment, and admin-istration by inhalation along with use of molnupiravir in antiviral combination therapy.
Medicine and Pharmacology, Pharmacology and Toxicology
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