2. Academic Validation
  3. Severe fever with thrombocytopenia syndrome virus (SFTSV)-host interactome screen identifies viral nucleoprotein-associated host factors as potential antiviral targets

Severe fever with thrombocytopenia syndrome virus (SFTSV)-host interactome screen identifies viral nucleoprotein-associated host factors as potential antiviral targets

  • Comput Struct Biotechnol J. 2021 Oct 1:19:5568-5577. doi: 10.1016/j.csbj.2021.09.034.
Jianli Cao 1,  Gang Lu 2 3 4 5,  Lei Wen 1,  Peng Luo 1,  Yaoqiang Huang 1,  Ronghui Liang 1,  Kaiming Tang 1,  Zhenzhi Qin 1,  Chris Chun-Yiu Chan 1,  Kenn Ka-Heng Chik 1,  Jiang Du 2 3 4 5,  Feifei Yin 2 3 4 5,  Zi-Wei Ye 1,  Hin Chu 1,  Dong-Yan Jin 6,  Kwok-Yung Yuen 1 3 4 7,  Jasper Fuk-Woo Chan 1 3 4 7,  Shuofeng Yuan 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  • 2 Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, Hainan 571199, China.
  • 3 Academician Workstation of Hainan Province, Hainan Medical University, Haikou, Hainan 571199, China.
  • 4 Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  • 5 Department of Pathogen Biology, Hainan Medical University, Haikou, Hainan 571199, China.
  • 6 School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  • 7 Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
PMID: 34712400 DOI: 10.1016/j.csbj.2021.09.034
Abstract

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.

Keywords

Artenimol; Bunyavirales; Interactome; Omacetaxine mepesuccinate; Pathogenesis; SFTSV; Treatment.

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