1. Berbamine hydrochloride potently inhibits SARS-CoV-2 infection by blocking S protein-mediated membrane fusion.
- Author
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Zhang, Zhe-Rui, Zhang, Ya-Nan, Zhang, Hong-Qing, Zhang, Qiu-Yan, Li, Na, Li, Qi, Deng, Cheng-Lin, Zhang, Bo, Li, Xiao-Dan, and Ye, Han-Qing
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MEMBRANE fusion , *CHIMERIC proteins , *SARS-CoV-2 , *CELL fusion , *VIRAL proteins , *MOLECULAR docking - Abstract
COVID-19 caused by SARS-CoV-2 has posed a significant threat to global public health since its outbreak in late 2019. Although there are a few drugs approved for clinical treatment to combat SARS-CoV-2 infection currently, the severity of the ongoing global pandemic still urges the efforts to discover new antiviral compounds. As the viral spike (S) protein plays a key role in mediating virus entry, it becomes a potential target for the design of antiviral drugs against COVID-19. Here, we tested the antiviral activity of berbamine hydrochloride, a bis-benzylisoquinoline alkaloid, against SARS-CoV-2 infection. We found that berbamine hydrochloride could efficiently inhibit SARS-CoV-2 infection in different cell lines. Further experiments showed berbamine hydrochloride inhibits SARS-CoV-2 infection by targeting the viral entry into host cells. Moreover, berbamine hydrochloride and other bis-benzylisoquinoline alkaloids could potently inhibit S-mediated cell-cell fusion. Furthermore, molecular docking results implied that the berbamine hydrochloride could bind to the post fusion core of SARS-CoV-2 S2 subunit. Therefore, berbamine hydrochloride may represent a potential efficient antiviral agent against SARS-CoV-2 infection. Author summary: The recent COVID-19 pandemic has caused a global health threat. Development of antiviral agents are urgently required to control the pandemic. In this study, we evaluated the antiviral activity of berbamine hydrochloride, a bis-benzylisoquinoline alkaloid that is isolated from traditional Chinese medicinal Berberis amurensis. We demonstrated that berbamine hydrochloride potently inhibits SARS-CoV-2 infection by blocking the entry of the virus into the host cell. Moreover, berbamine hydrochloride and other bis-benzylisoquinoline alkaloids also block SARS-CoV-2 S-mediated membrane fusion. Furthermore, we analyzed the interaction of berbamine hydrochloride and viral proteins by molecular docking analysis. We found that berbamine hydrochloride could directly bind to the post fusion core of SARS-CoV-2 S2 subunit, which mediates the fusion with the host membranes. Our results provide a new lead compound for antiviral agents against SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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