Identification and characterization of anti-chikungunya virus compounds using a biosafe toolkit

Yang Gao; Guojie Wang; Hanhua Zhang; Sicheng Tian; Yanqun Wang; Jincun Zhao; Xing Liu; Rong Ye; Rong Zhang

doi:10.1016/j.virs.2026.08.005

August 2026

Citation: Yang Gao, Guojie Wang, Hanhua Zhang, Sicheng Tian, Yanqun Wang, Jincun Zhao, Xing Liu, Rong Ye, Rong Zhang. Identification and characterization of anti-chikungunya virus compounds using a biosafe toolkit .VIROLOGICA SINICA, 2026, 41(4) : 779-790. http://dx.doi.org/10.1016/j.virs.2026.08.005

Identification and characterization of anti-chikungunya virus compounds using a biosafe toolkit

Yang Gao ^a ,
Guojie Wang ^a ,
Hanhua Zhang ^b ,
Sicheng Tian ^a ,
Yanqun Wang ^c ,
Jincun Zhao ^c ,
Xing Liu ^{b
,,} ,
Rong Ye ^{a
,,} ,
Rong Zhang ^{a
,,}

a. Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China;
b. Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen 518060, China;
c. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China

Corresponding author: Xing Liu, xingliu1@szu.edu.cn
Rong Ye, yerong24@fudan.edu.cn
Rong Zhang, rong_zhang@fudan.edu.cn
Received Date: 30 April 2026
Accepted Date: 06 August 2026
Available online: 10 August 2026

Abstract

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus for which no specific antiviral therapy is currently available. During the large outbreak in Foshan, Guangdong Province, China, in July 2025, CHIKV rapidly spread to neighboring regions and caused more than 16,000 confirmed cases. In this study, the predominant outbreak strain of CHIKV was selected as the reference sequence to establish a panel of complementary biosafe tools for antiviral compound screening and mechanistic investigation. A virus replicon particle (VRP) system for CHIKV was first constructed and applied to compound library screening, resulting in the identification of three candidate antiviral compounds: MDL-12330A, bazedoxifene acetate, and anidulafungin. To further validate their antiviral activities and investigate their potential mechanisms, CHIKV functional evaluation systems were subsequently established, including vesicular stomatitis virus (VSV)- and murine leukemia virus (MLV)-based pseudovirus systems for viral entry, a replicon RNA system for post-entry replication-associated processes, a replication-defective nsP4 mutant replicon RNA system for primary translation, and a virus-like particle (VLP) system for viral particle assembly and budding assessment. Using these complementary systems, we systematically evaluated the antiviral profiles of the three candidate compounds across multiple stages of the CHIKV life cycle. This analysis revealed distinct stage-specific inhibitory patterns and provided insights into their potential antiviral mechanisms, which warrant validation using authentic CHIKV infection to assess their translational potential.
- Chikungunya virus (CHIKV)
- , Antiviral compound
- , Pseudovirus
- , Viral replicon particle
- , Replicon RNA

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