Dihydropyridine-derived calcium channel blocker as a promising anti-hantavirus entry inhibitor

Bin Wang; Jiawei Pei; Hui Zhang; Jia Li; Yamei Dang; He Liu; Yuan Wang; Liang Zhang; Libin Qi; Yuewu Yang; Linfeng Cheng; Yangchao Dong; Airong Qian; Zhikai Xu; Yingfeng Lei; Fanglin Zhang; Wei Ye

doi:10.3389/fphar.2022.940178

Dihydropyridine-derived calcium channel blocker as a promising anti-hantavirus entry inhibitor

Front Pharmacol. 2022 Aug 29:13:940178. doi: 10.3389/fphar.2022.940178. eCollection 2022.

Authors

Bin Wang¹, Jiawei Pei^{2

3}, Hui Zhang², Jia Li⁴, Yamei Dang², He Liu², Yuan Wang², Liang Zhang², Libin Qi⁵, Yuewu Yang⁵, Linfeng Cheng², Yangchao Dong², Airong Qian³, Zhikai Xu², Yingfeng Lei², Fanglin Zhang², Wei Ye²

Affiliations

¹ Center of Clinical Aerospace Medicine, Airforce Medical University: Fourth Military Medical University, Xi'an, Shaanxi, China.
² Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi'an, Shaanxi, China.
³ Bone Metabolism Lab, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, China.
⁴ Department of Neurology, Xi'an International Medical Center Hospital, Xi'an, China.
⁵ Student Brigade, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi'an, Shaanxi, China.

Abstract

Hantaviruses, the causative agent for two types of hemorrhagic fevers, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), are distributed from Eurasia to America. HFRS and HPS have mortality rates of up to 15% or 45%, respectively. Currently, no certified therapeutic has been licensed to treat hantavirus infection. In this study, we discovered that benidipine hydrochloride, a calcium channel blocker, inhibits the entry of hantaviruses in vitro. Moreover, an array of calcium channel inhibitors, such as cilnidipine, felodipine, amlodipine, manidipine, nicardipine, and nisoldipine, exhibit similar antiviral properties. Using pseudotyped vesicular stomatitis viruses harboring the different hantavirus glycoproteins, we demonstrate that benidipine hydrochloride inhibits the infection by both HFRS- and HPS-causing hantaviruses. The results of our study indicate the possibility of repurposing FDA-approved calcium channel blockers for the treatment of hantavirus infection, and they also indicate the need for further research in vivo.

Keywords: Hantaan virus; antivirals; benidipine hydrochloride; bunyavirales; calcium channel blocker; hantavirus; hantavirus pulmonary syndrome; hemorrhagic fever with renal syndrome.