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Keywords = Huaiyangshan banyangvirus

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17 pages, 1778 KiB  
Article
Vascular Leak and Hypercytokinemia Associated with Severe Fever with Thrombocytopenia Syndrome Virus Infection in Mice
by Jonna B. Westover, Brady T. Hickerson, Arnaud J. Van Wettere, Brett L. Hurst, Jacqueline P. Kurz, Ashley Dagley, Petra Wülfroth, Takashi Komeno, Yousuke Furuta, Thomas Steiner and Brian B. Gowen
Pathogens 2019, 8(4), 158; https://doi.org/10.3390/pathogens8040158 - 21 Sep 2019
Cited by 15 | Viewed by 4845
Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever (VHF) endemic to China, South Korea, Japan, and Vietnam. Here we characterize the pathogenesis and natural history of disease in IFNAR-/- mice challenged with the HB29 strain of SFTS virus [...] Read more.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever (VHF) endemic to China, South Korea, Japan, and Vietnam. Here we characterize the pathogenesis and natural history of disease in IFNAR-/- mice challenged with the HB29 strain of SFTS virus (SFTSV) and demonstrate hallmark features of VHF such as vascular leak and high concentrations of proinflammatory cytokines in blood and tissues. Treatment with FX06, a natural plasmin digest product of fibrin in clinical development as a treatment for vascular leak, reduced vascular permeability associated with SFTSV infection but did not significantly improve survival outcome. Further studies are needed to assess the role of vascular compromise in the SFTS disease process modeled in IFNAR-/- mice. Full article
(This article belongs to the Special Issue Comparative Animal Models of Human Viral Infections)
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13 pages, 5434 KiB  
Article
Screening of an FDA-Approved Drug Library with a Two-Tier System Identifies an Entry Inhibitor of Severe Fever with Thrombocytopenia Syndrome Virus
by 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 and Kwok-Yung Yuen
Viruses 2019, 11(4), 385; https://doi.org/10.3390/v11040385 - 25 Apr 2019
Cited by 23 | Viewed by 7416
Abstract
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 [...] Read more.
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 hexachlorophene with the hydrophobic pocket between domain I and domain III of the SFTSV Gc glycoprotein was highly stable. The novel antiviral activity and mechanism of hexachlorophene in this study would facilitate the use of hexachlorophene as a lead compound to develop more entry inhibitors with higher anti-SFTSV potency and lower toxicity. Full article
(This article belongs to the Special Issue Viral Entry Pathways)
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