2. Academic Validation
  3. Decanoyl-Arg-Val-Lys-Arg-Chloromethylketone: An Antiviral Compound That Acts against Flaviviruses through the Inhibition of Furin-Mediated prM Cleavage

Decanoyl-Arg-Val-Lys-Arg-Chloromethylketone: An Antiviral Compound That Acts against Flaviviruses through the Inhibition of Furin-Mediated prM Cleavage

  • Viruses. 2019 Oct 31;11(11):1011. doi: 10.3390/v11111011.
Muhammad Imran 1 2 3 4,  Muhammad Kashif Saleemi 5,  Zheng Chen 6 7 8,  Xugang Wang 9 10 11,  Dengyuan Zhou 12 13 14,  Yunchuan Li 15 16 17,  Zikai Zhao 18 19 20,  Bohan Zheng 21 22 23,  Qiuyan Li 24 25 26,  Shengbo Cao 27 28 29,  Jing Ye 30 31 32
Affiliations

Affiliations

  • 1 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 2 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 3 The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 4 Department of Pathology, Faculty of Veterinary Science, University of Agriculture, Faisalabad 38040, Pakistan. [email protected].
  • 5 Department of Pathology, Faculty of Veterinary Science, University of Agriculture, Faisalabad 38040, Pakistan. [email protected].
  • 6 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 7 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 8 The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 9 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 10 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 11 The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 12 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 13 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 14 The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 15 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 16 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 17 The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 18 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 19 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 20 The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 21 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 22 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 23 The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 24 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 25 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 26 The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 27 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 28 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 29 The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 30 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 31 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
  • 32 The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China. [email protected].
PMID: 31683742 DOI: 10.3390/v11111011
Abstract

Flaviviruses, such as Zika virus (ZIKV), Japanese encephalitis virus (JEV), Dengue virus (DENV), and West Nile virus (WNV), are important arthropod-borne pathogens that present an immense global health problem. Their unpredictable disease severity, unusual clinical features, and severe neurological manifestations underscore an urgent need for Antiviral interventions. Furin, a host proprotein convertase, is a key contender in processing Flavivirus prM protein to M protein, turning the inert virus to an infectious particle. For this reason, the current study was planned to evaluate the Antiviral activity of decanoyl-Arg-Val-Lys-Arg-chloromethylketone, a specific Furin inhibitor, against flaviviruses, including ZIKV and JEV. Analysis of Viral Proteins revealed a significant increase in the prM/E index of ZIKV or JEV in dec-RVKR-cmk-treated Vero cells compared to DMSO-treated control cells, indicating dec-RVKR-cmk inhibits prM cleavage. Plaque assay, qRT-PCR, and immunofluorescence assay revealed a strong Antiviral activity of dec-RVKR-cmk against ZIKV and JEV in terms of the reduction in virus progeny titer and in viral RNA and protein production in both mammalian cells and mosquito cells. Time-of-drug addition assay revealed that the maximum reduction of virus titer was observed in post-infection treatment. Furthermore, our results showed that dec-RVKR-cmk exerts its inhibitory action on the virus release and next round infectivity but not on viral RNA replication. Taken together, our study highlights an interesting Antiviral activity of dec-RVKR-cmk against flaviviruses.

Keywords

Japanese encephalitis virus; Zika virus; flavivirus; furin inhibitor; precursor membrane protein.

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