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Kim, Tai Young
인지 및 사회성 연구단
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Platycodin D, a natural component of Platycodon grandiflorum, prevents both lysosome- and TMPRSS2-driven SARS-CoV-2 infection by hindering membrane fusion

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Title
Platycodin D, a natural component of Platycodon grandiflorum, prevents both lysosome- and TMPRSS2-driven SARS-CoV-2 infection by hindering membrane fusion
Author(s)
Tai Young Kim; Jeon, Sangeun; Jang, Youngho; Gotina, Lizaveta; Joungha Won; Yeon Ha Ju; Sunpil Kim; Minwoo Wendy Jang; Woojin Won; Mingu Gordon Park; Pae, Ae Nim; Han, Sunkyu; Kim, Seungtaek; C. Justin Lee
Publication Date
2021-05
Journal
Experimental and Molecular Medicine, v.53, no.5, pp.956 - 972
Publisher
Springer Nature
Abstract
© 2021, The Author(s).An ongoing pandemic of coronavirus disease 2019 (COVID-19) is now the greatest threat to global public health. Herbal medicines and their derived natural products have drawn much attention in the treatment of COVID-19, but the detailed mechanisms by which natural products inhibit SARS-CoV-2 have not been elucidated. Here, we show that platycodin D (PD), a triterpenoid saponin abundant in Platycodon grandiflorum (PG), a dietary and medicinal herb commonly used in East Asia, effectively blocks the two main SARS-CoV-2 infection routes via lysosome- and transmembrane protease serine 2 (TMPRSS2)-driven entry. Mechanistically, PD prevents host entry of SARS-CoV-2 by redistributing membrane cholesterol to prevent membrane fusion, which can be reinstated by treatment with a PD-encapsulating agent. Furthermore, the inhibitory effects of PD are recapitulated by the pharmacological inhibition or gene silencing of NPC1, which is mutated in patients with Niemann–Pick type C (NPC) displaying disrupted membrane cholesterol distribution. Finally, readily available local foods or herbal medicines containing PG root show similar inhibitory effects against SARS-CoV-2 infection. Our study proposes that PD is a potent natural product for preventing or treating COVID-19 and that briefly disrupting the distribution of membrane cholesterol is a potential novel therapeutic strategy for SARS-CoV-2 infection.
URI
https://pr.ibs.re.kr/handle/8788114/9888
DOI
10.1038/s12276-021-00624-9
ISSN
1226-3613
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > 1. Journal Papers (저널논문)
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