COVID-19 is caused by a novel coronavirus, the severe acute respiratory syndrome coronavirus (CoV)-2 (SARS-CoV-2). The virus is responsible for an ongoing pandemic and concomitant public health crisis around the world. While vaccine development is proving to be highly successful, parallel drug development approaches are also critical in the response to SARS-CoV-2 and other emerging viruses. Coronaviruses require Ca²⁺ ions for host cell entry, and we have previously shown that Ca²⁺ modulates the interaction of the viral fusion peptide with host cell membranes. In an attempt to accelerate drug repurposing, we tested a panel of L-type calcium channel blocker (CCB) drugs currently developed for other conditions to determine whether they would inhibit SARS-CoV-2 infection in cell culture. All the CCBs tested showed varying degrees of inhibition, with felodipine and nifedipine strongly limiting SARS-CoV-2 entry and infection in epithelial lung cells at concentrations where cell toxicity was minimal. Further studies with pseudotyped particles displaying the SARS-CoV-2 spike protein suggested that inhibition occurs at the level of virus entry. Overall, our data suggest that certain CCBs have the potential to treat SARS-CoV-2 infections and are worthy of further examination for possible treatment of COVID-19.

中文翻译：

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L 型钙通道抑制剂显示出通过防止病毒进入和传播来治疗 SARS-CoV-2 感染的治疗潜力

COVID-19 是由一种新型冠状病毒——严重急性呼吸综合征冠状病毒 (CoV)-2 (SARS-CoV-2) 引起的。该病毒是造成世界各地持续流行和随之而来的公共卫生危机的原因。虽然疫苗开发被证明非常成功，但并行药物开发方法对于应对 SARS-CoV-2 和其他新兴病毒也至关重要。冠状病毒需要Ca ²⁺离子才能进入宿主细胞，我们之前已经证明Ca ²⁺调节病毒融合肽与宿主细胞膜的相互作用。为了加速药物的重新利用，我们测试了一组目前针对其他病症开发的 L 型钙通道阻滞剂 (CCB) 药物，以确定它们是否会抑制细胞培养中的 SARS-CoV-2 感染。所有测试的 CCB 均显示出不同程度的抑制作用，其中非洛地平和硝苯地平在细胞毒性最小的浓度下强烈限制 SARS-CoV-2 进入上皮肺细胞并感染。对展示 SARS-CoV-2 刺突蛋白的假型颗粒的进一步研究表明，抑制发生在病毒进入的水平。总体而言，我们的数据表明某些 CCB 具有治疗 SARS-CoV-2 感染的潜力，并且值得进一步研究以用于治疗 COVID-19。