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Microorganisms
Volume 10
Issue 8
10.3390/microorganisms10081639
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Article

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

by
Frauke Assmus
1,2,†,
Jean-Sélim Driouich
3,†,
Rana Abdelnabi
4,†,
Laura Vangeel
4,†,
Franck Touret
3,†,
Ayorinde Adehin
1,2,
Palang Chotsiri
1,
Maxime Cochin
3,
Caroline S. Foo
4,
Dirk Jochmans
4,
Seungtaek Kim
5,
Léa Luciani
3,
Grégory Moureau
3,
Soonju Park
5,
Paul-Rémi Pétit
3,
David Shum
5,
Thanaporn Wattanakul
1,
Birgit Weynand
6,
Laurent Fraisse
7,
Jean-Robert Ioset
7,
Charles E. Mowbray
7,
Andrew Owen
8,
Richard M. Hoglund
1,2,
Joel Tarning
1,2,
Xavier de Lamballerie
3,
Antoine Nougairède
3,
Johan Neyts
4,9,
Peter Sjö
7,
Fanny Escudié
7,*,
Ivan Scandale
7,* and
Eric Chatelain
7,*add Show full author list remove Hide full author list
1
Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
2
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LG, UK
3
Unité des Virus Émergents (UVE), Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 190-Inserm 1207, 13005 Marseille, France
4
Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
5
Institut Pasteur Korea, 16, Daewangpangyo-ro 712 beon-gil, Bundang-gu, Seongnam-si 13488, Korea
6
Departmet of Imaging and Pathology, Katholieke Universiteit Leuven, Translational Cell and Tissue Research, 3000 Leuven, Belgium
7
Drugs for Neglected Diseases Initiative (DNDi), 1202 Geneva, Switzerland
8
Centre for Excellence in Long-Acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 7ZX, UK
9
Global Virus Network (GVN), Baltimore, MD 21201, USA
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Microorganisms 2022, 10(8), 1639; https://doi.org/10.3390/microorganisms10081639
Submission received: 7 July 2022 / Revised: 3 August 2022 / Accepted: 4 August 2022 / Published: 12 August 2022
(This article belongs to the Special Issue SARS-CoV-2/COVID-19: Infection Models, Therapeutics and Vaccines)
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Abstract

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.
Keywords: COVID-19; drug repurposing; translational medicine; pandemics; clinical trials COVID-19; drug repurposing; translational medicine; pandemics; clinical trials

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MDPI and ACS Style

Assmus, F.; Driouich, J.-S.; Abdelnabi, R.; Vangeel, L.; Touret, F.; Adehin, A.; Chotsiri, P.; Cochin, M.; Foo, C.S.; Jochmans, D.; et al. Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19. Microorganisms 2022, 10, 1639. https://doi.org/10.3390/microorganisms10081639

AMA Style

Assmus F, Driouich J-S, Abdelnabi R, Vangeel L, Touret F, Adehin A, Chotsiri P, Cochin M, Foo CS, Jochmans D, et al. Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19. Microorganisms. 2022; 10(8):1639. https://doi.org/10.3390/microorganisms10081639

Chicago/Turabian Style

Assmus, Frauke, Jean-Sélim Driouich, Rana Abdelnabi, Laura Vangeel, Franck Touret, Ayorinde Adehin, Palang Chotsiri, Maxime Cochin, Caroline S. Foo, Dirk Jochmans, and et al. 2022. "Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19" Microorganisms 10, no. 8: 1639. https://doi.org/10.3390/microorganisms10081639

APA Style

Assmus, F., Driouich, J.-S., Abdelnabi, R., Vangeel, L., Touret, F., Adehin, A., Chotsiri, P., Cochin, M., Foo, C. S., Jochmans, D., Kim, S., Luciani, L., Moureau, G., Park, S., Pétit, P.-R., Shum, D., Wattanakul, T., Weynand, B., Fraisse, L., ... Chatelain, E. (2022). Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19. Microorganisms, 10(8), 1639. https://doi.org/10.3390/microorganisms10081639

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