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

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

doi:10.1371/journal.ppat.1010343

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

PLoS Pathog. 2022 Feb 17;18(2):e1010343. doi: 10.1371/journal.ppat.1010343. eCollection 2022 Feb.

Authors

Xinxin Wang¹, Jie Luo¹, Zhiyuan Wen¹, Lei Shuai¹, Chong Wang¹, Gongxun Zhong¹, Xijun He¹, Huizhen Cao¹, Renqiang Liu¹, Jinying Ge¹, Ronghong Hua¹, Ziruo Sun¹, Xijun Wang¹, Jinliang Wang¹, Zhigao Bu^{1

2}

Affiliations

¹ State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China.
² Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, P. R. China.

Abstract

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 Cav1.2 pore-forming subunit (Cav1.2 α1c) 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. Cav1.2 α1c 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 Cav1.2 α1c is a promising target for antiviral drug development for COVID-19.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

A549 Cells
Animals
COVID-19 Drug Treatment*
COVID-19* / pathology
COVID-19* / virology
Cells, Cultured
Chlorocebus aethiops
Diltiazem / pharmacology*
Diltiazem / therapeutic use
Disease Models, Animal
Female
HEK293 Cells
HeLa Cells
Humans
Lung / drug effects*
Lung / pathology
Lung / virology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
SARS-CoV-2 / drug effects*
SARS-CoV-2 / physiology
Vero Cells
Virus Attachment / drug effects
Virus Internalization / drug effects

Substances

Diltiazem

Grants and funding

The work was supported by the National Key Research and Development Program of China (2021YFC2301700, LS), (2020YFC0846500, ZB), (2018YFC1200601, XW) and (2020YFC0841100, ZB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.