한빛사논문
- 조회70
Min Heui Yoo a, Han Young Eom a, Wan-Jung Im a, Byoung-Seok Lee a, Kang-Hyun Han a, Joung-Wook Seo a, Yunha Hwang b, Jihyun Youm b,c, Sangho Lee b,d, Seungtaek Kim e, Kyong-Cheol Ko f, Yong-Bum Kim a
aDepartment of Advanced Toxicology Research, Korea Institute of Toxicology, Daejeon 34114, South Korea
bResearch Institute, Dong-Wha Pharmaceutical Company, Yongin City 17084, South Korea
cGraduate School of East-West Medical Science, Kyung Hee University, Yongin City 17104, South Korea
dSchool of Pharmacy, Sungkyunkwan University, Suwon City 16419, South Korea
eZoonotic Virus Laboratory, Institute Pasteur Korea, Seongnam City 13488, South Korea
fKorea Preclinical Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, South Korea
Corresponding author : Yong-Bum Kim
Abstract
Background: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, remarkable advances have been made in vaccine development to reduce mortality. However, therapeutic interventions for COVID-19 are comparatively limited despite these intensive efforts. Furthermore, the rapid mutation capability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a characteristic of its RNA structure, has led to the emergence of multiple variants, necessitating a shift from a predominantly vaccine-centric approach to one that encompasses therapeutic strategies. 6'-Hydroxy justicidin B (6'-HJB), an arylnaphthalene lignan isolated from Justicia procumbens, a traditional Chinese medicine, is known for its antiviral properties.
Hypothesis/purpose: The aim of the present study was to assess the effectiveness and safety of 6'-HJB against SARS-CoV-2 in order to determine its potential as a therapeutic agent against COVID-19.
Methods: The efficacy of 6'-HJB was evaluated both in vitro using Vero and Calu-3 cell lines and in vivo using ferrets. The safety assessment included toxicokinetics, safety pharmacology, and Good Laboratory Practice (GLP)-compliant toxicity evaluations following single- and repeated-dose toxicity studies in dogs.
Results: The anti-SARS-CoV-2 efficacy of 6'-HJB was evaluated through dose-response curve (DRC) analysis using immunofluorescence; 6'-HJB demonstrated superior inhibition of SARS-CoV-2 growth and lower cytotoxicity than remdesivir. In SARS-CoV-2-infected ferret, 6'-HJB showed efficacy comparable to that of the positive control, Truvada. Further GLP toxicity studies corroborated the safety profile of 6'-HJB. Single-dose and 4-week repeated oral toxicity studies in Beagle dogs demonstrated minimal harmful effects at the highest dosages. The lethal dose of 6'-HJB exceeded 2,000 mg kg-1 in Beagle dogs. Toxicokinetic and GLP safety pharmacology studies demonstrated no adverse effects of 6'-HJB on metabolic processes, respiratory or central nervous systems, or cardiac functions.
Conclusion: This research highlights both the antiviral efficacy and safety profile of 6'-HJB, underscoring its potential as a novel COVID-19 treatment option. The potential of 6'-HJB was demonstrated using modern scientific methodologies and standards.
논문정보
- Research article
- 2024년 08월 (BRIC 등록일 2024-09-12)
- 국내 연구진
- 의약학 > 종양의학
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