Diltiazem inhibits SARS-CoV-2 cell attachment and internalization and decreases the viral infection in mouse lung

文献类型： 外文期刊

第一作者： Wang, Xinxin

作者： Wang, Xinxin;Luo, Jie;Wen, Zhiyuan;Shuai, Lei;Wang, Chong;Zhong, Gongxun;He, Xijun;Cao, Huizhen;Liu, Renqiang;Ge, Jinying;Hua, Ronghong;Sun, Ziruo;Wang, Xijun;Wang, Jinliang;Bu, Zhigao;Bu, Zhigao

作者机构：

期刊名称：PLOS PATHOGENS （ 影响因子：7.464； 五年影响因子：7.913 ）

ISSN： 1553-7366

年卷期： 2022 年 18 卷 2 期

页码：

收录情况： SCI

摘要： Author summaryThe emergence of variants of SARS-CoV-2 and the breakthrough infections that have occurred in recipients of approved SARS-CoV-2 vaccines raise doubts about the effectiveness of the vaccines and highlight the importance of antiviral drugs. An ideal drug to treat COVID-19 should be safe, affordable, and accessible. However, remdesivir remains the only authorized drug approved by the US FDA for emergency use, and it appears to have little effect on hospitalized COVID-19 patients. Therefore, identifying drugs to treat SARS-CoV-2 infections remains extremely important and urgent. In this study, we found that the calcium channel blocker diltiazem, which has been approved in the US since 1982 and is cheap and widely used in clinical practice for many indications, inhibits the binding and internalization of SARS-CoV-2, and decreases SARS-CoV-2 infection in cells and mouse lung. The L-type calcium channel Ca(v)1.2 pore-forming subunit (Ca(v)1.2 alpha(1c)), the main target of diltiazem, interacts and colocalizes with SARS-CoV-2 spike protein and ACE2, thereby affecting cell attachment and internalization of SARS-CoV-2. Our finding suggests that diltiazem could be candidate COVID-19 treatment and that Ca(v)1.2 alpha(1c) may be a promising target for anti-SARS-CoV-2 drugs. The continuous emergence of severe acute respiratory coronavirus 2 (SARS-CoV-2) variants and the increasing number of breakthrough infection cases among vaccinated people support the urgent need for research and development of antiviral drugs. Viral entry is an intriguing target for antiviral drug development. We found that diltiazem, a blocker of the L-type calcium channel Ca(v)1.2 pore-forming subunit (Ca(v)1.2 alpha(1c)) and an FDA-approved drug, inhibits the binding and internalization of SARS-CoV-2, and decreases SARS-CoV-2 infection in cells and mouse lung. Ca(v)1.2 alpha(1c) interacts with SARS-CoV-2 spike protein and ACE2, and affects the attachment and internalization of SARS-CoV-2. Our finding suggests that diltiazem has potential as a drug against SARS-CoV-2 infection and that Ca(v)1.2 alpha(1c) is a promising target for antiviral drug development for COVID-19.

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