IJMS, Vol. 26, Pages 2912: Glycyl-tRNA Synthetase as a Target for Antiviral Drug Screening Against Influenza Virus

International Journal of Molecular Sciences doi: 10.3390/ijms26072912

Authors:
Jingjing Zhang
Xiaorong Li
Jingxian Liang
Xinru Meng
Chenchen Zhu
Guangpu Yang
Yali Liang
Qikai Zhou
Qianni Qin
Zan Li
Ting Zhang
Gen Liu
Litao Sun

Influenza viruses are characterized by their high variability and pathogenicity, and effective therapeutic options remain limited. Given these challenges, targeting host cell proteins that facilitate viral replication presents a promising strategy for antiviral drug discovery. In the present study, we observed a significant upregulation of Glycyl-tRNA synthetase (GlyRS) within 24 h post-PR8 virus infection. The inhibition of GlyRS expression in A549 cells resulted in a marked reduction in infection rates across multiple influenza virus strains, while the overexpression of GlyRS led to an increase in viral infectivity during the early stages of infection. These findings suggest that GlyRS plays a critical role in the replication of influenza virus. Accordingly, we screened for potential inhibitors targeting GlyRS and identified Lycobetaine and Scutellarein using a multifaceted approach. Through a combination of molecular dynamics simulations, we further elucidated the mechanisms of action and potential binding sites of these compounds. Both inhibitors effectively suppressed the replication of influenza viruses, and their antiviral activity was confirmed to be mediated by GlyRS targeting. Therefore, GlyRS inhibitors, such as Lycobetaine and Scutellarein, represent promising candidates for combating influenza infections and provide novel insights into the treatment of influenza and aaRS-related diseases, opening new avenues for the development of aaRS-targeted therapeutics.

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Jingjing Zhang www.mdpi.com