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Calcium Channel Blockers Reduce Severe Fever With Thrombocytopenia Syndrome Virus (SFTSV) Related Fatality

Calcium Channel Blockers Reduce Severe Fever With Thrombocytopenia Syndrome Virus (SFTSV) Related Fatality

Hao Li, Lei-Ke Zhang, Shu-Fen Li, Shao-Fei Zhang, Wei-Wei Wan, Yu-Lan Zhang, Qi-Lin Xin, Ke Dai, Yuan-Yuan Hu, Zhi-Bo Wang, Xiang-Tao Zhu, Yu-Jie Fang, Ning Cui, Pan-He Zhang, Chun Yuan, Qing-Bin Lu, Jie-Ying Bai, etc.

Cell Res. 2019 Sep;29(9):739-753.

PMID: 31444469

Abstract:

Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne infectious disease caused by a novel phlebovirus (SFTS virus, SFTSV), was listed among the top 10 priority infectious diseases by the World Health Organization due to its high fatality of 12%-50% and possibility of pandemic transmission. Currently, effective anti-SFTSV intervention remains unavailable. Here, by screening a library of FDA-approved drugs, we found that benidipine hydrochloride, a calcium channel blocker (CCB), inhibited SFTSV replication in vitro. Benidipine hydrochloride was revealed to inhibit virus infection through impairing virus internalization and genome replication. Further experiments showed that a broad panel of CCBs, including nifedipine, inhibited SFTSV infection. The anti-SFTSV effect of these two CCBs was further analyzed in a humanized mouse model in which CCB treatment resulted in reduced viral load and decreased fatality rate. Importantly, by performing a retrospective clinical investigation on a large cohort of 2087 SFTS patients, we revealed that nifedipine administration enhanced virus clearance, improved clinical recovery, and remarkably reduced the case fatality rate by >5-fold. These findings are highly valuable for developing potential host-oriented therapeutics for SFTS and other lethal acute viral infections known to be inhibited by CCBs in vitro.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP91599745	Benidipine hydrochloride		91599-74-5	Price

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