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Dual Effects of 3-epi-betulin from Daphniphyllum glaucescens in Suppressing SARS-CoV-2-Induced Inflammation and Inhibiting Virus Entry.
Yeh, Yung-Ju; Chao, Tai-Ling; Chang, Yu-Jen; Chang, Sui-Yuan; Lu, Chih-Hao; Chao, Chih-Hua; Su, Wen-Chi; Tseng, Ching-Ping; Lai, Michael M C; Cheng, Ju-Chien.
Afiliação
  • Yeh YJ; Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404328, Taiwan.
  • Chao TL; Research Center for Emerging Viruses, China Medical University Hospital, Taichung 404328, Taiwan.
  • Chang YJ; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei 100229, Taiwan.
  • Chang SY; The Ph.D. Program of Biotechnology and Biomedical Industry, China Medical University, Taichung 404328, Taiwan.
  • Lu CH; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei 100229, Taiwan.
  • Chao CH; Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College Medicine, Taipei 100229, Taiwan.
  • Su WC; Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu 300093, Taiwan.
  • Tseng CP; Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu 300093, Taiwan.
  • Lai MMC; School of Pharmacy, China Medical University, Taichung 4060404, Taiwan.
  • Cheng JC; Research Center for Emerging Viruses, China Medical University Hospital, Taichung 404328, Taiwan.
Int J Mol Sci ; 24(23)2023 Dec 01.
Article em En | MEDLINE | ID: mdl-38069363
The continuous emergence of SARS-CoV-2 variants has led to a protracted global COVID-19 pandemic with significant impacts on public health and global economy. While there are currently available SARS-CoV-2 vaccines and therapeutics, most of the FDA-approved antiviral agents directly target viral proteins. However, inflammation is the initial immune pathogenesis induced by SARS-CoV-2 infection, there is still a need to find additional agents that can control the virus in the early stages of infection to alleviate disease progression for the next pandemic. Here, we find that both the spike protein and its receptor CD147 are crucial for inducing inflammation by SARS-CoV-2 in THP-1 monocytic cells. Moreover, we find that 3-epi-betulin, isolated from Daphniphyllum glaucescens, reduces the level of proinflammatory cytokines induced by SARS-CoV-2, consequently resulting in a decreased viral RNA accumulation and plaque formation. In addition, 3-epi-betulin displays a broad-spectrum inhibition of entry of SARS-CoV-2 pseudoviruses, including Alpha (B.1.1.7), Eplison (B.1.429), Gamma (P1), Delta (B.1.617.2) and Omicron (BA.1). Moreover, 3-epi-betulin potently inhibits SARS-CoV-2 infection with an EC50 of <20 µM in Calu-3 lung epithelial cells. Bioinformatic analysis reveals the chemical interaction between the 3-epi-betulin and the spike protein, along with the critical amino acid residues in the spike protein that contribute to the inhibitory activity of 3-epi-betulin against virus entry. Taken together, our results suggest that 3-epi-betulin exhibits dual effect: it reduces SARS-CoV-2-induced inflammation and inhibits virus entry, positioning it as a potential antiviral agent against SARS-CoV-2.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Daphniphyllum / COVID-19 Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Taiwan

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Daphniphyllum / COVID-19 Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Taiwan