Targeting the Cav1.2-KCa1.1 axis prevents rabies virus internalization and protects against lethal infection.

Authors

Ziruo Sun, Jinqiu Wang, Zhiyuan Wen, Lei Shuai, Wenjing Sun, Mengjie Yang, Jinyu Wang, Junyu Chen, Tengteng Mi, Xianjing Zhou, Peiran Zhou, Nannan Lv, Zhenbo Zhao, Jinying Ge, Weiye Chen, Xijun Wang, Chong Wang, Zhigao Bu, Jinliang Wang

Published in

PLoS pathogens. Volume 22. Issue 10. Pages e1014675. Oct 06, 2026. Epub Oct 06, 2026.

Abstract

Rabies is an almost always fatal disease caused by rabies virus (RABV). Once RABV enters the central nervous system, the mortality rate is almost 100%. Therefore, preventing RABV from entering the nervous system is crucial for the development of anti-RABV therapeutics. Here, we found that the L-type calcium channel Cav1.2 pore-forming subunit (Cav1.2) and potassium calcium-activated channel subfamily M alpha 1 (KCa1.1) are involved in the internalization of RABV using an siRNA approach. RABV glycoprotein interacts with Cav1.2, a process that is required for the subsequent activation of the channel. The activated Cav1.2 then interacts with and activates KCa1.1 to regulate the endocytosis of RABV by promoting the F-actin polymerization. Importantly, diltiazem, a blocker of Cav1.2 and an FDA-approved drug, has been shown to substantially reduce mortality in mice infected with RABV. Approximately 70% of mice survived following treatment with diltiazem at 50 mg/kg, whereas the 25 mg/kg dose resulted in 26% survival. Our findings suggest that Cav1.2 is a promising target for the development of antiviral drugs against rabies and enhances our comprehension of the RABV entry mechanism.

PMID:
42837418
Bibliographic data and abstract were imported from PubMed on 07 Oct 2026.

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