한빛사 논문
Joo‑Eun Lee1†, Se Yun Jeong2†, Zijun Li1,3†, Hyun‑Yi Kim4, Hyun‑Woo Kim5, Min Jeong Yoo2, Hee Joo Jang2, Do‑Kyun Kim5, Namki Cho1, Hee Min Yoo3,6* and Ki Hyun Kim2*
1College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea.
2School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
3Biometrology Group, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, Republic of Korea.
4NGeneS Inc., Ansan 15495, Republic of Korea.
5Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Republic of Korea.
6Department of Precision Measurement, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
†Joo-Eun Lee, Se Yun Jeong and Zijun Li contributed equally to this work.
*Correspondence: Hee Min Yoo, Ki Hyun Kim
Abstract
Background: Natural products can serve as one of the alternatives, exhibiting high potential for the treatment and prevention of COVID-19, caused by SARS-CoV-2. Herein, we report a screening platform to test the antiviral efficacy of a natural product library against SARS-CoV-2 and verify their activity using lung organoids.
Methods: Since SARS-CoV-2 is classified as a risk group 3 pathogen, the drug screening assay must be performed in a biosafety level 3 (BSL-3) laboratory. To circumvent this limitation, pseudotyped viruses (PVs) have been developed as replacements for the live SARS-CoV-2. We developed PVs containing spikes from Delta and Omicron variants of SARS-CoV-2 and improved the infection in an angiotensin-converting enzyme 2 (ACE2)-dependent manner. Human induced pluripotent stem cells (hiPSCs) derived lung organoids were generated to test the SARS-CoV-2 therapeutic efficacy of natural products.
Results: Flavonoids from our natural product library had strong antiviral activity against the Delta- or Omicron-spike-containing PVs without affecting cell viability. We aimed to develop strategies to discover the dual function of either inhibiting infection at the beginning of the infection cycle or reducing spike stability following SARS-CoV-2 infection. When lung cells are already infected with the virus, the active flavonoids induced the degradation of the spike protein and exerted anti-inflammatory effects. Further experiments confirmed that the active flavonoids had strong antiviral activity in lung organoid models.
Conclusion: This screening platform will open new paths by providing a promising standard system for discovering novel drug leads against SARS-CoV-2 and help develop promising candidates for clinical investigation as potential therapeutics for COVID-19.
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