J Med Virol . Three Salvianolic acids inhibit 2019-nCoV spike pseudovirus viropexis by binding to both its RBD and receptor ACE2

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J Med Virol


. 2021 Feb 12.
doi: 10.1002/jmv.26874. Online ahead of print.
Three Salvianolic acids inhibit 2019-nCoV spike pseudovirus viropexis by binding to both its RBD and receptor ACE2


Shiling Hu ^{1 2} , Jue Wang ^{1 2} , Yongjing Zhang ^{1 2} , Haoyun Bai ^{1 2} , Cheng Wang ^{1 2} , Nan Wang ^{1 2} , Langchong He ^{1 2}



Affiliations

• PMID: 33580518
• DOI: 10.1002/jmv.26874

Abstract

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

Keywords: 2019-nCoV; ACE2; Salvianolic acid A; Salvianolic acid B; Salvianolic acid C.