Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19
Issued Date
2022-08-01
Resource Type
eISSN
20762607
Scopus ID
2-s2.0-85137342033
Journal Title
Microorganisms
Volume
10
Issue
8
Rights Holder(s)
SCOPUS
Bibliographic Citation
Microorganisms Vol.10 No.8 (2022)
Suggested Citation
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., Ioset J.R., Mowbray C.E., Owen A., Hoglund R.M., Tarning J., Lamballerie X.d., Nougairède A., Neyts J., Sjö P., Escudié F., Scandale I., Chatelain E. Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19. Microorganisms Vol.10 No.8 (2022). doi:10.3390/microorganisms10081639 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/84934
Title
Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19
Author(s)
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.
Ioset J.R.
Mowbray C.E.
Owen A.
Hoglund R.M.
Tarning J.
Lamballerie X.d.
Nougairède A.
Neyts J.
Sjö P.
Escudié F.
Scandale I.
Chatelain E.
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.
Ioset J.R.
Mowbray C.E.
Owen A.
Hoglund R.M.
Tarning J.
Lamballerie X.d.
Nougairède A.
Neyts J.
Sjö P.
Escudié F.
Scandale I.
Chatelain E.
Author's Affiliation
Faculty of Tropical Medicine, Mahidol University
Departement Microbiologie, Immunologie en Transplantatie
Departement Beeldvorming & Pathologie
Aix Marseille Université
Institut Pasteur Korea
University of Liverpool
Nuffield Department of Medicine
Drugs for Neglected Diseases initiative (DNDi)
Global Virus Network
Departement Microbiologie, Immunologie en Transplantatie
Departement Beeldvorming & Pathologie
Aix Marseille Université
Institut Pasteur Korea
University of Liverpool
Nuffield Department of Medicine
Drugs for Neglected Diseases initiative (DNDi)
Global Virus Network
Other Contributor(s)
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.