Viruses, Vol. 11, Pages 385: Screening of an FDA-Approved Drug Library with a Two-Tier System Identifies an Entry Inhibitor of Severe Fever with Thrombocytopenia Syndrome Virus

Viruses, Vol. 11, Pages 385: Screening of an FDA-Approved Drug Library with a Two-Tier System Identifies an Entry Inhibitor of Severe Fever with Thrombocytopenia Syndrome Virus Viruses doi: 10.3390/v11040385 Authors: Shuofeng Yuan Jasper Fuk-Woo Chan Zi-Wei Ye Lei Wen Terance Gi-Wai Tsang Jianli Cao Jingjing Huang Chris Chun-Yiu Chan Kenn Ka-Heng Chik Garnet Kwan-Yue Choi Jian-Piao Cai Feifei Yin Hin Chu Mifang Liang Dong-Yan Jin Kwok-Yung Yuen Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe disease in humans with case-fatality rates of up to 30%. There are currently very limited treatment options for SFTSV infection. We conducted a drug repurposing program by establishing a two-tier test system to rapidly screen a Food and Drug Administration- (FDA)-approved drug library for drug compounds with anti-SFTSV activity in vitro. We identified five drug compounds that inhibited SFTSV replication at low micromolar concentrations, including hexachlorophene, triclosan, regorafenib, eltrombopag, and broxyquinoline. Among them, hexachlorophene was the most potent with an IC50 of 1.3 ± 0.3 µM and a selectivity index of 18.7. Mechanistic studies suggested that hexachlorophene was a virus entry inhibitor, which impaired SFTSV entry into host cells by interfering with cell membrane fusion. Molecular docking analysis predicted that the binding of hexachlorophe...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research