Calcium channel blockers reduce severe fever with thrombocytopenia syndrome virus (SFTSV) related fatality

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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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Data availability

The data that support the findings of this study are available from the corresponding authors upon request.


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This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29010204), the National Natural Science Foundation of China (81825019, 81722041, 31770188, 81472005, 81473023 and 31500144), the National Science and Technology Major Project (2018ZX10101004001005), the National Key R&D Program of China (2016YFC1200400, 2018YFA0507201 and 2016YFC1201905), the Hundred Talents Program of the Chinese Academy of Sciences (K.P.), the Youth Innovation Promotion Association of the Chinese Academy of Sciences (2018367), the Special Major Program of Wuhan Institute of Virology (WIV-135-TP1), the State Key Laboratory of Virology Open Projects (2017IOV003), the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81621005), and the New Star Plan of Science and Technology of Beijing (Z171100001117089).

Author information

K.P. and W.L. conceived and supervised the study. H.L., L.-K.Z., K.P. and W.L. designed the experiments, analyzed the results, and wrote the manuscript. H.L., L.-K.Z., S.-F.L., W.-W.W., Y.-L.Z., Q.-L.X., K.D., Y.-Y.H., X.-T.Z., Y.-J.F., P.-H.Z., J.-Y.B. and K.P. performed the experiments. H.L., S.-F.Z., Z.-B.W., N.C., C.Y. and W.L. recruited the patients. H.L., L.-K.Z., S.-F.Z. and Q.-B.L. performed statistical analysis. G.-F.X. and F.D. contributed to the design of the study and data analysis. All authors had access to the study data, and reviewed and approved the final manuscript.

Correspondence to Wei Liu or Ke Peng.

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