Sainan Wang Defended her PhD Thesis

Congratulations to Sainan Wang, who successfully defended her PhD thesis “Structure-guided insights into the functions of CHIKV nsP2”.

The aim of this study was to enhance the understanding of the function of CHIKV nsP2 in viral RNA replication, with a specific focus on its N-terminal domain and the flexible linker between the N- and C-terminal domains.

Alphaviruses are small, enveloped viruses with positive-strand RNA genomes, known for causing significant human and animal diseases globally, except in Antarctica. These arboviruses are transmitted primarily through Aedes and Culex mosquito vectors and include notable pathogens like chikungunya virus (CHIKV), o’nyong-nyong virus (ONNV), and Eastern equine encephalitis virus (EEEV), among others. CHIKV, in particular, is infamous for causing chikungunya fever, characterized by severe joint pain that can become chronic, with millions of cases reported worldwide since its first outbreak in 1952. Despite its global health impact, there are no licensed treatments for CHIKV infections.

Alphavirus replication relies on the complex activities of nonstructural proteins (nsPs), especially nsP2, which plays a pivotal role in RNA synthesis and modification. nsP2 is bifunctional; its N-terminal region is involved in RNA helicase and other activities necessary for replication, while the C-terminal has protease activity crucial for processing viral polyproteins into functional replication complexes. This study focused on CHIKV nsP2, particularly its N-terminal domain and the flexible linker between the N- and C-terminal domains, revealing critical residues essential for viral RNA replication. Alterations in these regions can significantly impact viral replication, offering insights into potential antiviral targets and vaccine development. Furthermore, the research highlighted the adaptability of CHIKV in incorporating G3BP/Rin binding motifs into nsP2, supporting replication in both mammalian and insect cells, underscoring the complex interplay of structural and functional elements within nsP2 crucial for alphavirus replication and pathogenesis.

PhD Thesis is available here: https://dspace.ut.ee/server/api/core/bitstreams/f8d20ff3-55fc-4806-86bd-61fbcba16a5c/content