Three salvianolic acids inhibit 2019-nCoV spike pseudovirus viropexis by binding to both its RBD and receptor ACE2.

作者: Cheng Wang , Langchong He , Nan Wang , Jue Wang , Yongjing Zhang

DOI: 10.1002/JMV.26874

关键词: Flow cytometryReceptorCaffeic acidSalvia miltiorrhizaMolecular biologyChemistryEnzymeCoronavirusHEK 293 cellsPlasma protein bindingVirology

摘要: Since December 2019, the new coronavirus [also known as severe acute respiratory syndrome 2 (SARS-CoV-2, 2019-nCoV)]- induced disease, COVID-19, has spread rapidly worldwide. Studies have reported that traditional Chinese medicine Salvia miltiorrhiza possesses remarkable antiviral properties; however, anti-coronaviral activity of its main components, salvianolic acid A (SAA), B (SAB), and C (SAC) is still debated. In this study, we used Cell Counting Kit-8 staining flow cytometry to evaluate toxicity SAA, SAB, SAC on ACE2 (angiotensin-converting enzyme 2) high-expressing HEK293T cells (ACE2h cells). We found SAB had a minor effect viability ACE2h at concentrations below 100 μM. further evaluated binding capacity spike protein 2019-nCoV using molecular docking surface plasmon resonance (SPR). They could bind receptor-binding domain (RBD) with constant (KD ) (3.82±0.43) e-6 M, (5.15±0.64)e-7 (2.19±0.14)e-6 M; KD (4.08±0.61)e-7 (2.95±0.78)e-7 M (7.32±0.42)e-7M, respectively. As result, were determined inhibit entry Spike pseudovirus EC50 11.31μM, 6.22 μM, 10.14 μM cells, conclusion, our study revealed three Salvianolic acids can into by RBD protein. This article protected copyright. All rights reserved.

参考文章(33)
S. Belouzard, V. C. Chu, G. R. Whittaker, Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 106, pp. 5871- 5876 ,(2009) , 10.1073/PNAS.0809524106
Fang Li, Wenhui Li, Michael Farzan, Stephen C Harrison, Structure of SARS Coronavirus Spike Receptor-Binding Domain Complexed with Receptor Science. ,vol. 309, pp. 1864- 1868 ,(2005) , 10.1126/SCIENCE.1116480
Daohua Xu, Liangliang Xu, Chenhui Zhou, Wayne Y.W. Lee, Tie Wu, Liao Cui, Gang Li, Salvianolic acid B promotes osteogenesis of human mesenchymal stem cells through activating ERK signaling pathway The International Journal of Biochemistry & Cell Biology. ,vol. 51, pp. 1- 9 ,(2014) , 10.1016/J.BIOCEL.2014.03.005
Lanying Du, Yuxian He, Yusen Zhou, Shuwen Liu, Bo-Jian Zheng, Shibo Jiang, The spike protein of SARS-CoV — a target for vaccine and therapeutic development Nature Reviews Microbiology. ,vol. 7, pp. 226- 236 ,(2009) , 10.1038/NRMICRO2090
Hao Huang, Lanxin Ji, Shengyou Song, Jing Wang, Na Wei, Min Jiang, Gang Bai, Guoan Luo, Identification of the major constituents in Xuebijing injection by HPLC-ESI-MS. Phytochemical Analysis. ,vol. 22, pp. 330- 338 ,(2011) , 10.1002/PCA.1284
Norihiro Kokudo, Wei Tang, Dingzhi Fang, Xiaoyan Cui, Yueling Wang, Traditional Chinese medicine and related active compounds against hepatitis B virus infection. BioScience Trends. ,vol. 4, pp. 39- 47 ,(2010)
Qiao Zhang, Shifeng Wang, Yangyang Yu, Shengnan Sun, Yuxin Zhang, Yanling Zhang, Wei Yang, Shiyou Li, Yanjiang Qiao, Salvianolic Acid A, as a Novel ETA Receptor Antagonist, Shows Inhibitory Effects on Tumor in Vitro. International Journal of Molecular Sciences. ,vol. 17, pp. 1244- ,(2016) , 10.3390/IJMS17081244
Rodrigo Delvecchio, Luiza Higa, Paula Pezzuto, Ana Valadão, Patrícia Garcez, Fábio Monteiro, Erick Loiola, André Dias, Fábio Silva, Matthew Aliota, Elizabeth Caine, Jorge Osorio, Maria Bellio, David O’Connor, Stevens Rehen, Renato de Aguiar, Andrea Savarino, Loraine Campanati, Amilcar Tanuri, Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models Viruses. ,vol. 8, pp. 322- ,(2016) , 10.3390/V8120322
Lihua Zuo, Zhi Sun, Yurong Hu, Ya Sun, Wenhua Xue, Lin Zhou, Jun Zhang, Xiaoyue Bao, Zhenfeng Zhu, Guanglu Suo, Xiaojian Zhang, Rapid determination of 30 bioactive constituents in XueBiJing injection using ultra high performance liquid chromatography-high resolution hybrid quadrupole-orbitrap mass spectrometry coupled with principal component analysis. Journal of Pharmaceutical and Biomedical Analysis. ,vol. 137, pp. 220- 228 ,(2017) , 10.1016/J.JPBA.2017.01.024
Yan He, Kun Jia, Lei Li, Qi Wang, Shuhui Zhang, Jiaming Du, Heng Du, Salvianolic acid B attenuates mitochondrial stress against Aβ toxicity in primary cultured mouse neurons Biochemical and Biophysical Research Communications. ,vol. 498, pp. 1066- 1072 ,(2018) , 10.1016/J.BBRC.2018.03.119