Berbamine prevents SARS-CoV-2 entry and transmission

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2024-11-08 DOI:10.1016/j.isci.2024.111347

Srikanth Sadhu , Sandeep Goswami , Ritika Khatri , Bharat Lohiya , Virendra Singh , Rahul Yadav , Vinayaka Das , Manas Ranjan Tripathy , Prabhanjan Dwivedi , Mitul Srivastava , Shailendra Mani , Shailendra Asthana , Sweety Samal , Amit Awasthi

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引用次数: 0

Abstract

Effective antiviral drugs are essential to combat COVID-19 and future pandemics. Although many compounds show antiviral in vitro activity, only a few retain effectiveness in vivo against SARS-CoV-2. Here, we show that berbamine (Berb) is effective against SARS-CoV, MER-CoV, SARS-CoV-2 and its variants, including the XBB.1.16 variant. In hACE2.Tg mice, Berb suppresses SARS-CoV-2 replication through two distinct mechanisms: inhibiting spike-mediated viral entry and enhancing antiviral gene expression during infection. The administration of Berb, in combination with remdesivir (RDV), clofazimine (Clof) and fangchinoline (Fcn), nearly eliminated viral load and promoted recovery from acute SARS-CoV-2 infection and its variants. Co-housed mice in direct contact with either pre-treated or untreated infected mice exhibited negligible viral loads, reduced lung pathology, and decreased viral shedding, suggesting that Berb may effectively hinder virus transmission. This broad-spectrum activity positions Berb as a promising preventive or therapeutic option against betacoronaviruses.

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小檗胺可预防 SARS-CoV-2 的进入和传播

有效的抗病毒药物对于抗击 COVID-19 和未来的流行病至关重要。尽管许多化合物在体外显示出抗病毒活性，但只有少数化合物在体内对 SARS-CoV-2 保持有效。在这里，我们发现小檗胺（Berb）对 SARS-CoV、MER-CoV、SARS-CoV-2 及其变种（包括 XBB.1.16 变种）有效。在 hACE2.Tg 小鼠中，Berb 通过两种不同的机制抑制 SARS-CoV-2 的复制：抑制尖峰介导的病毒进入和增强感染期间的抗病毒基因表达。将 Berb 与雷米地韦（RDV）、氯法齐明（Clof）和方胆啉（Fcn）联合使用，几乎可以消除病毒载量，促进急性 SARS-CoV-2 感染及其变种的恢复。与预处理或未处理的感染小鼠直接接触的同舍小鼠的病毒载量可忽略不计，肺部病理变化减轻，病毒脱落减少，这表明 Berb 可有效阻止病毒传播。这种广谱活性使 Berb 成为一种很有前景的预防或治疗 betacoronaviruses 的选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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