Molnupiravir combined with different repurposed drugs further inhibits SARS-CoV-2 infection in human nasal epithelium in vitro

Autor: Hulda R. Jonsdottir, Denise Siegrist, Thomas Julien, Blandine Padey, Mendy Bouveret, Olivier Terrier, Andres Pizzorno, Song Huang, Kirandeep Samby, Timothy N.C. Wells, Bernadett Boda, Manuel Rosa-Calatrava, Olivier B. Engler, Samuel Constant
Přispěvatelé: Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2022
Předmět:
Zdroj: Biomedicine and Pharmacotherapy
Biomedicine and Pharmacotherapy, 2022, 150, pp.113058. ⟨10.1016/j.biopha.2022.113058⟩
Jonsdottir, Hulda R; Siegrist, Denise; Julien, Thomas; Padey, Blandine; Bouveret, Mendy; Terrier, Olivier; Pizzorno, Andres; Huang, Song; Samby, Kirandeep; Wells, Timothy N C; Boda, Bernadett; Rosa-Calatrava, Manuel; Engler, Olivier B; Constant, Samuel (2022). Molnupiravir combined with different repurposed drugs further inhibits SARS-CoV-2 infection in human nasal epithelium in vitro. Biomedicine & pharmacotherapy, 150, p. 113058. Elsevier 10.1016/j.biopha.2022.113058
ISSN: 1950-6007
0753-3322
Popis: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in late 2019, has caused a worldwide pandemic with unprecedented economic and societal impact. Currently, several vaccines are available, and multitudes of antiviral treatments have been proposed and tested. Although many of the vaccines show high clinical efficacy, they are not equally accessible worldwide. Additionally, due to the continuous emergence of new virus variants, and generally short duration of immunity, the development of safe and effective antiviral treatments remains of the utmost importance. Since the emergence of SARS-CoV-2, substantial efforts have been undertaken to repurpose existing and approved drugs for accelerated clinical testing and potential emergency use authorizations. However, drug-repurposing using high throughput screenings in cellular assays, often identify hits that later prove ineffective in clinical studies. Our approach was to evaluate the activity of compounds that have either been tested clinically or already undergone extensive preclinical profiling, using a standardized in vitro model of human nasal epithelium. Secondly, we evaluated drug combinations using sub-maximal doses of each active single compound. Here, we report the antiviral effects of 95 single compounds and 30 combinations. The data show that selected drug combinations including 10 μM of molnupiravir, a viral RNA-dependent RNA polymerase (RdRp) inhibitor, effectively inhibit SARS-CoV-2 replication. This indicates that such combinations are worthy of further evaluation as potential treatment strategies against coronavirus disease 2019 (COVID-19).
Databáze: OpenAIRE
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