title: Antiviral activity of selected flavonoids against Chikungunya virus.
abstract: This study focuses on the antiviral activity of selected flavonoids against the Chikungunya virus (CHIKV), a mosquito-transmitted virus that can cause incapacitating arthritis in infected individuals. Based on the results of screening on Vero cells, the tested compounds were evaluated further with various assays, including cytotoxicity assay, virus yield assay by quantitative reverse transcription polymerase chain reaction (qRT-PCR), virus RNA replication assay with a CHIKV replicon cell line, Western blotting, and quantitative immunofluorescence assay. Baicalein, fisetin, and quercetagetin displayed potent inhibition of CHIKV infection, with 50% inhibitory concentrations [IC50] of 1.891 μg/ml (6.997 μM), 8.444 μg/ml (29.5 μM), and 13.85 μg/ml (43.52 μM), respectively, and with minimal cytotoxicity. The time-of-addition studies and various antiviral assays demonstrated that baicalein and quercetagetin mainly inhibited CHIKV binding to the Vero cells and displayed potent activity against extracellular CHIKV particles. The qRT-PCR, immunofluorescence assay, and Western blot analyses indicated that each of these flavonoids affects CHIKV RNA production and viral protein expression. These data provide the first evidence of the intracellular anti-CHIKV activity of baicalein, fisetin, and quercetagetin.
authors.affiliation: Tropical Infectious Disease Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
authors.forename: Rafidah
authors.initials: R
authors.lastname: Lani
authors.affiliation: Tropical Infectious Disease Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
authors.forename: Pouya
authors.initials: P
authors.lastname: Hassandarvish
authors.affiliation: Tropical Infectious Disease Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
authors.forename: Meng-Hooi
authors.initials: MH
authors.lastname: Shu
authors.affiliation: Tropical Infectious Disease Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
authors.forename: Wai Hong
authors.initials: WH
authors.lastname: Phoon
authors.affiliation: Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Justin Jang Hann
authors.initials: JJ
authors.lastname: Chu
authors.affiliation: Biosecurity Research Institute, Kansas State University, Manhattan, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Higgs
authors.affiliation: Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Vanlandingham
authors.affiliation: Tropical Infectious Disease Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
authors.forename: Sazaly
authors.initials: S
authors.lastname: Abu Bakar
authors.affiliation: Tropical Infectious Disease Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia. Electronic address: keivan@um.edu.my.
authors.forename: Keivan
authors.initials: K
authors.lastname: Zandi
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology; D002460:Cell Line; D002646:Chikungunya virus / Q000187:drug effects* / Q000235:genetics; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005838:Genotype; D020128:Inhibitory Concentration 50; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D001688:Biological Products; D005419:Flavonoids
keywords: Antiviral effect; Chikungunya virus; Flavonoids; Natural compounds