Establishment of multicenter COVID-19 therapeutics preclinical test system in Republic of Korea - 20/05/23
Abstract |
Throughout the recent COVID-19 pandemic, South Korea led national efforts to develop vaccines and therapeutics for SARS-CoV-2. The project proceeded as follows: 1) evaluation system setup (including Animal Biosafety Level 3 (ABSL3) facility alliance, standardized nonclinical evaluation protocol, and laboratory information management system), 2) application (including committee review and selection), and 3) evaluation (including expert judgment and reporting). After receiving 101 applications, the selection committee reviewed pharmacokinetics, toxicity, and efficacy data and selected 32 final candidates. In the nonclinical efficacy test, we used golden Syrian hamsters and human angiotensin-converting enzyme 2 transgenic mice under a cytokeratin 18 promoter to evaluate mortality, clinical signs, body weight, viral titer, neutralizing antibody presence, and histopathology. These data indicated eight new drugs and one repositioned drug having significant efficacy for COVID-19. Three vaccine and four antiviral drugs exerted significant protective activities against SARS-CoV-2 pathogenesis. Additionally, two anti-inflammatory drugs showed therapeutic effects on lung lesions and weight loss through their mechanism of action but did not affect viral replication. Along with systematic verification of COVID-19 animal models through large-scale studies, our findings suggest that ABSL3 multicenter alliance and nonclinical evaluation protocol standardization can promote reliable efficacy testing against COVID-19, thus expediting medical product development.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Highlights |
• | In recent COVID-19 pandemic situation, we established a multicenter COVID-19 efficacy evaluation system. |
• | After receiving 101 applications, the selection committee reviewed and selected 32 final candidates. |
• | Mortality, body weight, viral titer, neutralizing antibody, and histopathology were evaluated in nonclinical efficacy test. |
• | Three vaccines, four antiviral drugs, and two anti-inflammatory drugs showed significant efficacy against COVID-19. |
Keywords : SARS-CoV-2, COVID-19, Nonclinical, hACE2 mouse, Golden Syrian hamster
Abbreviations : ABSL3, COVID-19, SARS-CoV-2, ACE2, TMPRSS2, MOAs, DMEM, FBS, TCID50, PFU, CPE, H&E, LIMS, PK, dpi, NHPs, CCSP, SFTPB
Plan
Vol 80
Article 102189- juin 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.