Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19
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, ba...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/10/8/1639 |
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| author | Frauke Assmus Jean-Sélim Driouich Rana Abdelnabi Laura Vangeel Franck Touret Ayorinde Adehin Palang Chotsiri Maxime Cochin Caroline S. Foo Dirk Jochmans Seungtaek Kim Léa Luciani Grégory Moureau Soonju Park Paul-Rémi Pétit David Shum Thanaporn Wattanakul Birgit Weynand Laurent Fraisse Jean-Robert Ioset Charles E. Mowbray Andrew Owen Richard M. Hoglund Joel Tarning Xavier de Lamballerie Antoine Nougairède Johan Neyts Peter Sjö Fanny Escudié Ivan Scandale Eric Chatelain |
| author_facet | Frauke Assmus Jean-Sélim Driouich Rana Abdelnabi Laura Vangeel Franck Touret Ayorinde Adehin Palang Chotsiri Maxime Cochin Caroline S. Foo Dirk Jochmans Seungtaek Kim Léa Luciani Grégory Moureau Soonju Park Paul-Rémi Pétit David Shum Thanaporn Wattanakul Birgit Weynand Laurent Fraisse Jean-Robert Ioset Charles E. Mowbray Andrew Owen Richard M. Hoglund Joel Tarning Xavier de Lamballerie Antoine Nougairède Johan Neyts Peter Sjö Fanny Escudié Ivan Scandale Eric Chatelain |
| author_sort | Frauke Assmus |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T12:54:10Z |
| format | Article |
| id | doaj.art-a9ef2617e75845fa98746d7ddae47ef7 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-09T12:54:10Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-a9ef2617e75845fa98746d7ddae47ef72023-11-30T22:02:18ZengMDPI AGMicroorganisms2076-26072022-08-01108163910.3390/microorganisms10081639Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19Frauke Assmus0Jean-Sélim Driouich1Rana Abdelnabi2Laura Vangeel3Franck Touret4Ayorinde Adehin5Palang Chotsiri6Maxime Cochin7Caroline S. Foo8Dirk Jochmans9Seungtaek Kim10Léa Luciani11Grégory Moureau12Soonju Park13Paul-Rémi Pétit14David Shum15Thanaporn Wattanakul16Birgit Weynand17Laurent Fraisse18Jean-Robert Ioset19Charles E. Mowbray20Andrew Owen21Richard M. Hoglund22Joel Tarning23Xavier de Lamballerie24Antoine Nougairède25Johan Neyts26Peter Sjö27Fanny Escudié28Ivan Scandale29Eric Chatelain30Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, ThailandUnité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, FranceLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, BelgiumLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, BelgiumUnité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, FranceMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, ThailandMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, ThailandUnité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, FranceLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, BelgiumLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, BelgiumInstitut Pasteur Korea, 16, Daewangpangyo-ro 712 beon-gil, Bundang-gu, Seongnam-si 13488, KoreaUnité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, FranceUnité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, FranceInstitut Pasteur Korea, 16, Daewangpangyo-ro 712 beon-gil, Bundang-gu, Seongnam-si 13488, KoreaUnité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, FranceInstitut Pasteur Korea, 16, Daewangpangyo-ro 712 beon-gil, Bundang-gu, Seongnam-si 13488, KoreaMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, ThailandDepartmet of Imaging and Pathology, Katholieke Universiteit Leuven, Translational Cell and Tissue Research, 3000 Leuven, BelgiumDrugs for Neglected Diseases Initiative (DND<i>i</i>), 1202 Geneva, SwitzerlandDrugs for Neglected Diseases Initiative (DND<i>i</i>), 1202 Geneva, SwitzerlandDrugs for Neglected Diseases Initiative (DND<i>i</i>), 1202 Geneva, SwitzerlandCentre for Excellence in Long-Acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 7ZX, UKMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, ThailandMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, ThailandUnité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, FranceUnité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, FranceLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, BelgiumDrugs for Neglected Diseases Initiative (DND<i>i</i>), 1202 Geneva, SwitzerlandDrugs for Neglected Diseases Initiative (DND<i>i</i>), 1202 Geneva, SwitzerlandDrugs for Neglected Diseases Initiative (DND<i>i</i>), 1202 Geneva, SwitzerlandDrugs for Neglected Diseases Initiative (DND<i>i</i>), 1202 Geneva, SwitzerlandIn 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.https://www.mdpi.com/2076-2607/10/8/1639COVID-19drug repurposingtranslational medicinepandemicsclinical trials |
| spellingShingle | Frauke Assmus Jean-Sélim Driouich Rana Abdelnabi Laura Vangeel Franck Touret Ayorinde Adehin Palang Chotsiri Maxime Cochin Caroline S. Foo Dirk Jochmans Seungtaek Kim Léa Luciani Grégory Moureau Soonju Park Paul-Rémi Pétit David Shum Thanaporn Wattanakul Birgit Weynand Laurent Fraisse Jean-Robert Ioset Charles E. Mowbray Andrew Owen Richard M. Hoglund Joel Tarning Xavier de Lamballerie Antoine Nougairède Johan Neyts Peter Sjö Fanny Escudié Ivan Scandale Eric Chatelain Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19 Microorganisms COVID-19 drug repurposing translational medicine pandemics clinical trials |
| title | Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19 |
| title_full | Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19 |
| title_fullStr | Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19 |
| title_full_unstemmed | Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19 |
| title_short | Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19 |
| title_sort | need for a standardized translational drug development platform lessons learned from the repurposing of drugs for covid 19 |
| topic | COVID-19 drug repurposing translational medicine pandemics clinical trials |
| url | https://www.mdpi.com/2076-2607/10/8/1639 |
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