2. Academic Validation
  3. A sulfonamide chalcone inhibited dengue virus with a potential target at the SAM-binding site of viral methyltransferase

A sulfonamide chalcone inhibited dengue virus with a potential target at the SAM-binding site of viral methyltransferase

  • Antiviral Res. 2023 Dec:220:105753. doi: 10.1016/j.antiviral.2023.105753.
Van Cao 1,  I Putu Sukanadi 2,  Naphat Loeanurit 3,  Aphinya Suroengrit 3,  Wattamon Paunrat 4,  Vipanee Vibulakhaopan 5,  Kowit Hengphasatporn 6,  Yasuteru Shigeta 6,  Warinthorn Chavasiri 2,  Siwaporn Boonyasuppayakorn 7
Affiliations

Affiliations

  • 1 Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand; Interdisciplinary Program in Microbiology, Graduate School, Chulalongkorn University, Bangkok, 10330, Thailand; DaNang University of Medical Technology and Pharmacy, DaNang, 50200, Viet Nam.
  • 2 Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
  • 3 Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
  • 4 Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand; Interdisciplinary Program in Medical Sciences, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
  • 5 Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand; Department of Biology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
  • 6 Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
  • 7 Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand; Interdisciplinary Program in Microbiology, Graduate School, Chulalongkorn University, Bangkok, 10330, Thailand; Interdisciplinary Program in Medical Sciences, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand; Center of Excellence in Vaccine Research and Development, Chulalongkorn University (Chula-VRC), Bangkok, 10330, Thailand. Electronic address: [email protected].
PMID: 37967754 DOI: 10.1016/j.antiviral.2023.105753
Abstract

Dengue Infection is a global health problem as climate change facilitates the spread of mosquito vectors. Infected patients could progress to severe plasma leakage and hemorrhagic shock, where current standard treatment remains supportive. Previous reports suggested that several flavonoid derivatives inhibited mosquito-borne flaviviruses. This work aimed to explore sulfonamide chalcone derivatives as dengue inhibitors and to identify molecular targets. We initially screened 27 sulfonamide Chalcones using cell-based Antiviral and cytotoxic screenings. Two potential compounds, SC22 and SC27, were identified with DENV1-4 EC50s in the range of 0.71-0.94 and 3.15-4.46 μM, and CC50s at 14.63 and 31.02 μM, respectively. The compounds did not show any elevation in ALT or Cr in C57BL/6 mice on the 1st, 3rd, and 7th days after being administered intraperitoneally with 50 mg/kg SC22 or SC27 in a single dose. Moreover, the SAM-binding site of NS5 methyltransferase was a potential target of SC27 identified by computational and enzyme-based assays. The main target of SC22 was in a late stage of viral replication, but the exact target molecule had yet to be identified. In summary, a sulfonamide chalcone, SC27, was a potential DENV inhibitor that targeted viral methyltransferase. Further investigation should be the study of the structure-activity relationship of SC27 derivatives for higher potency and lower toxicity.

Keywords

Chalcone; Dengue; Flavonoid; Methyltransferase; Sulfonamide.

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