Journal
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
Volume 19, Issue -, Pages 5568-5577Publisher
ELSEVIER
DOI: 10.1016/j.csbj.2021.09.034
Keywords
Artenimol; Bunyavirales; Interactome; Omacetaxine mepesuccinate; Pathogenesis; SFTSV; Treatment
Funding
- Health and Medical Research Fund [CID-HKU1-10, 19180502]
- Food and Health Bureau
- Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for Department of Health of the Hong Kong Special Administrative Region Government
- Innovation and Technology Fund (ITF)
- The Government of the Hong Kong Special Administrative Region
- Government of the Hong Kong Special Administrative Region
- Sanming Project of Medicine in Shenzhen, China [SZSM201911014]
- High Level-Hospital Program, Health Commission of Guangdong Province, China
- Major Science and Technology Program of Hainan Province [ZDKJ202003]
- Hainan academician innovation platform [YSPTZX202004]
- Hainan talent development project [SRC200003]
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The study characterized the interaction between SFTSV and host proteins, identified drug compounds that could potentially inhibit SFTSV infection, with artenimol and omacetaxine mepesuccinate showing in vitro antiviral activity.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus that causes severe infection in humans characterized by an acute febrile illness with thrombocytopenia and hemorrhagic complications, and a mortality rate of up to 30%. Understanding on virus-host protein interactions may facilitate the identification of druggable antiviral targets. Herein, we utilized liquid chromatography-tandem mass spectrometry to characterize the SFTSV interactome in human embryonic kidney-derived permanent culture (HEK-293T) cells. We identified 445 host proteins that co-precipitated with the viral glycoprotein N, glycoprotein C, nucleoprotein, or nonstructural protein. A network of SFTSV-host protein interactions based on reduced viral fitness affected upon host factor down-regulation was then generated. Screening of the DrugBank database revealed numerous drug compounds that inhibited the prioritized host factors in this SFTSV interactome. Among these drug compounds, the clinically approved artenimol (an antimalarial) and omacetaxine mepesuccinate (a cephalotaxine) were found to exhibit anti-SFTSV activity in vitro. The higher selectivity of artenimol (71.83) than omacetaxine mepesuccinate (8.00) highlights artenimol's potential for further antiviral development. Mechanistic evaluation showed that artenimol interfered with the interaction between the SFTSV nucleoprotein and the host glucose-6-phosphate isomerase (GPI), and that omacetaxine mepesuccinate interfered with the interaction between the viral nucleoprotein with the host ribosomal protein L3 (RPL3). In summary, the novel interactomic data in this study revealed the virus-host protein interactions in SFTSV infection and facilitated the discovery of potential anti-SFTSV treatments. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
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