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Abstract Title:

[Salvianolic acid B and its magnesium salt inhibit SARS-CoV-2 infection of Vero-E6 cells by blocking spike protein-mediated membrane fusion].

Abstract Source:

Nan Fang Yi Ke Da Xue Xue Bao. 2021 Apr 20 ;41(4):475-482. PMID: 33963705

Abstract Author(s):

C Yang, C Cheng, J Wang, K Chen, J Zhan, X Pan, X Xu, W Xu, S Liu

Article Affiliation:

C Yang

Abstract:

OBJECTIVE: The investigate the inhibitory effects of the traditional Chinese medicine (TCM) monomer salvianolic acid B (Sal-B) and its magnesium salt Salvia Miltiorrhiza Polyphenolate Injection (ZDDY) against SARS-CoV-2 infectionand explore the molecular mechanism.

OBJECTIVE: The anti-SARS-CoV-2 activity of Sal-B and ZDDY was assessed using the authentic and pseudotyped SARS-CoV-2 infection assay. The antiviral targets of Sal-B were identified by molecular docking and molecular dynamics simulation. Circular dichroism spectroscopy was used to examine the structural characteristics of HR1 and HR2 regions of SARS-CoV-2 S protein, and the S protein-mediated cell-cell fusion assay was used to evaluate the effect of Sal-B on virus-cell membrane fusion. Flow cytometry was carried out to analyze the effect of Sal-B on the binding of SARS-CoV-2 RBD to hACE2 receptor.

OBJECTIVE: The median effective concentrations (EC) of Sal-B and ZDDY against SARSCoV-2 infection in Vero-E6 cells were 55.47μmol/L and 36.07 μg/mL, respectively. Both Sal-B and ZDDY successfully inhibited the entry of SARS-CoV-2 pseudovirus into the cells that stably expressed human ACE2 (ACE2/293T), with half maximal inhibitory concentrations (IC) of 1.69μmol/L and 24.81 μg/mL, respectively. Sal-B showed a binding affinity of -8.2 kcal/mol to the 6-helix bundle (6-HB) of SARS-CoV-2 S protein. Molecular dynamics simulation showed stable binding between Sal-B and the 6-HB of SARS-CoV-2 S protein at the predicted binding site. Sal-B disturbed the formation of the secondary structure of 6-HB in HR1P/HR2P mixture, resulting in a significantly lowered α-helicity (<0.05). Sal-B dose-dependently inhibited SARS-CoV-2 S protein-mediated cell-cell fusion, with an ICof 3.33μmol/L. Sal-B showed no effect on RBD-Fc protein binding to the ACE2 receptor.

OBJECTIVE: Sal-B and its magnesium salt ZDDY can inhibit the entry of SARS-CoV-2 in Vero-E6 cellsby blocking SARS-CoV-2 spike protein-mediated virus-cell membrane fusion.

Study Type : In Vitro Study

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