| Title | Calcium channel blockers reduce severe fever with thrombocytopenia syndrome virus (SFTSV) related fatality |
| Authors | Li, Hao Zhang, Lei-Ke Li, Shu-Fen Zhang, Shao-Fei Wan, Wei-Wei Zhang, Yu-Lan Xin, Qi-Lin Dai, Ke Hu, Yuan-Yuan Wang, Zhi-Bo Zhu, Xiang-Tao Fang, Yu-Jie Cui, Ning Zhang, Pan-He Yuan, Chun Lu, Qing-Bin Bai, Jie-Ying Deng, Fei Xiao, Geng-Fu Liu, Wei Peng, Ke |
| Affiliation | Beijing Inst Microbiol & Epidemiol, Beijing Key Lab Vector Borne & Nat Focus Infect D, State Key Lab Pathogen & Biosecur, Beijing 100071, Peoples R China Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Hubei, Peoples R China Univ Chinese Acad Sci, Beijing 100049, Peoples R China Chinese Acad Sci, Wuhan Natl Biosafety Lab, Mega Sci Ctr Biosafety Res, Wuhan 430071, Hubei, Peoples R China Peoples Liberat Army, Hosp 154, Xinyang, Henan, Peoples R China Peking Univ, Sch Publ Hlth, Beijing, Peoples R China Acad Mil Med Sci, Lab Anim Ctr, Beijing, Peoples R China |
| Issue Date | 2019 |
| Publisher | CELL RESEARCH |
| 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. |
| URI | http://hdl.handle.net/20.500.11897/545483 |
| ISSN | 1001-0602 |
| DOI | 10.1038/s41422-019-0214-z |
| Indexed | SCI(E) EI |
| Appears in Collections: | 公共卫生学院 |
