Establishment of multicenter COVID-19 therapeutics preclinical test system in Republic of Korea

Hyuna Noh, Suhyeon Yoon, Sung Hee Kim, Jiseon Kim, Jung Seon Seo, Jeong Jin Kim, In Ho Park, Jooyeon Oh, Joon Yong Bae, Gee Eun Lee, Sun Je Woo, Sun Min Seo, Na Won Kim, Youn Woo Lee, Hui Jeong Jang, Seung Min Hong, Se Hee An, Kwang Soo Lyoo, Minjoo Yeom, Hanbyeul LeeBud Jung, Sun Woo Yoon, Jung Ah Kang, Sang Hyuk Seok, Yu Jin Lee, Seo Yeon Kim, Young Been Kim, Ji Yeon Hwang, Dain On, Soo Yeon Lim, Sol Pin Kim, Ji Yun Jang, Ho Lee, Kyoungmi Kim, Hyo Jung Lee, Hong Bin Kim, Sun Bean Kim, Jun Won Park, Dae Gwin Jeong, Daesub Song, Kang Seuk Choi, Ho Young Lee, Yang Kyu Choi, Jung ah Choi, Manki Song, Man Seong Park, Jun Young Seo, Jeon Soo Shin, Jun Won Yun, Ki Taek Nam, Je Kyung Seong

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number102189
JournalPulmonary Pharmacology and Therapeutics
Volume80
DOIs
Publication statusPublished - 2023 Jun

Bibliographical note

Publisher Copyright:
© 2023

Keywords

  • COVID-19
  • Golden Syrian hamster
  • Nonclinical
  • SARS-CoV-2
  • hACE2 mouse

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)

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