Chikungunya virus nonstructural protein 1 as an antiviral target

Kovacikova, K. (2021)

Doctoral Thesis

This PhD thesis is dedicated to the development of novel antiviral agents against Chikungunya virus (CHIKV). CHIKV is a reemerging mosquito-borne virus causing an arthritis-like disease that is characterized by abrupt fever, malaise, and chronic joint and muscle pain. The high morbidity associated with Chikungunya fever and the negative impact on human health underscore the need to develop an effective antiviral therapy and other control measures.

This PhD thesis presents a series of experimental studies focused on the identification of novel small molecules with CHIKV inhibitory activity and the elucidation of their mode of action. The results in this thesis demonstrate that CHIKV nonstructural protein 1 (nsP1) represents a suitable target for antiviral drug development. In addition, the potential for developing combination therapy consisting of small molecule inhibitors with different targets for prevention and treatment of CHIKV infections has been explored.

• Chikungunya virus
• Alphavirus
• Nonstructural protein 1
• Small-molecule inhibitors
• RNA capping
• Antiviral target
• Antiviral drug screening
• Enzymatic assays

• All authors: Kovacikova, K.
• Supervisor: Snijder, E.J.
• Co-supervisor: Hemert, M.J. van
• Committee: Geluk, A.; Kuppeveld, F.J.M. van; Ahola, T.; Myeni, S.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2021-04-20
• ISBN (print): 9789464165104
• Sponsorship: The research described in this thesis was performed at the Department of Medical Microbiology of the Leiden University Medical Center, Leiden, the Netherlands and was funded by the Marie Sklodowska-Curie ETN European Training Network “ANTIVIRALS” (EU grant agreement 642434).