期刊
CELL RESEARCH
卷 29, 期 9, 页码 739-753出版社
SPRINGERNATURE
DOI: 10.1038/s41422-019-0214-z
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类别
资金
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB29010204]
- National Natural Science Foundation of China [81825019, 81722041, 31770188, 81472005, 81473023, 31500144]
- National Science and Technology Major Project [2018ZX10101004001005]
- National Key R&D Program of China [2016YFC1200400, 2018YFA0507201, 2016YFC1201905]
- Hundred Talents Program of the Chinese Academy of Sciences
- Youth Innovation Promotion Association of the Chinese Academy of Sciences [2018367]
- Special Major Program of Wuhan Institute of Virology [WIV-135-TP1]
- State Key Laboratory of Virology Open Projects [2017IOV003]
- Foundation for Innovative Research Groups of the National Natural Science Foundation of China [81621005]
- New Star Plan of Science and Technology of Beijing [Z171100001117089]
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.
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