Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19.

Autor: Assmus F; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LG, UK., Driouich JS; Unité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, France., Abdelnabi R; Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium., Vangeel L; Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium., Touret F; Unité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, France., Adehin A; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LG, UK., Chotsiri P; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand., Cochin M; Unité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, France., Foo CS; Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium., Jochmans D; Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium., Kim S; Institut Pasteur Korea, 16, Daewangpangyo-ro 712 beon-gil, Bundang-gu, Seongnam-si 13488, Korea., Luciani L; Unité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, France., Moureau G; Unité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, France., Park S; Institut Pasteur Korea, 16, Daewangpangyo-ro 712 beon-gil, Bundang-gu, Seongnam-si 13488, Korea., Pétit PR; Unité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, France., Shum D; Institut Pasteur Korea, 16, Daewangpangyo-ro 712 beon-gil, Bundang-gu, Seongnam-si 13488, Korea., Wattanakul T; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand., Weynand B; Departmet of Imaging and Pathology, Katholieke Universiteit Leuven, Translational Cell and Tissue Research, 3000 Leuven, Belgium., Fraisse L; Drugs for Neglected Diseases Initiative (DNDi), 1202 Geneva, Switzerland., Ioset JR; Drugs for Neglected Diseases Initiative (DNDi), 1202 Geneva, Switzerland., Mowbray CE; Drugs for Neglected Diseases Initiative (DNDi), 1202 Geneva, Switzerland., Owen A; Centre for Excellence in Long-Acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 7ZX, UK., Hoglund RM; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LG, UK., Tarning J; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LG, UK., Lamballerie X; Unité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, France., Nougairède A; Unité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, France., Neyts J; Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.; Global Virus Network (GVN), Baltimore, MD 21201, USA., Sjö P; Drugs for Neglected Diseases Initiative (DNDi), 1202 Geneva, Switzerland., Escudié F; Drugs for Neglected Diseases Initiative (DNDi), 1202 Geneva, Switzerland., Scandale I; Drugs for Neglected Diseases Initiative (DNDi), 1202 Geneva, Switzerland., Chatelain E; Drugs for Neglected Diseases Initiative (DNDi), 1202 Geneva, Switzerland.
Jazyk: angličtina
Zdroj: Microorganisms [Microorganisms] 2022 Aug 12; Vol. 10 (8). Date of Electronic Publication: 2022 Aug 12.
DOI: 10.3390/microorganisms10081639
Abstrakt: In the absence of drugs to treat or prevent COVID-19, drug repurposing can be a valuable strategy. Despite a substantial number of clinical trials, drug repurposing did not deliver on its promise. While success was observed with some repurposed drugs (e.g., remdesivir, dexamethasone, tocilizumab, baricitinib), others failed to show clinical efficacy. One reason is the lack of clear translational processes based on adequate preclinical profiling before clinical evaluation. Combined with limitations of existing in vitro and in vivo models, there is a need for a systematic approach to urgent antiviral drug development in the context of a global pandemic. We implemented a methodology to test repurposed and experimental drugs to generate robust preclinical evidence for further clinical development. This translational drug development platform comprises in vitro, ex vivo, and in vivo models of SARS-CoV-2, along with pharmacokinetic modeling and simulation approaches to evaluate exposure levels in plasma and target organs. Here, we provide examples of identified repurposed antiviral drugs tested within our multidisciplinary collaboration to highlight lessons learned in urgent antiviral drug development during the COVID-19 pandemic. Our data confirm the importance of assessing in vitro and in vivo potency in multiple assays to boost the translatability of pre-clinical data. The value of pharmacokinetic modeling and simulations for compound prioritization is also discussed. We advocate the need for a standardized translational drug development platform for mild-to-moderate COVID-19 to generate preclinical evidence in support of clinical trials. We propose clear prerequisites for progression of drug candidates for repurposing into clinical trials. Further research is needed to gain a deeper understanding of the scope and limitations of the presented translational drug development platform.
Databáze: MEDLINE
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