Glycyl-tRNA Synthetase as a Target for Antiviral Drug Screening Against Influenza Virus
Year: 2025
Type: article
Abstract: 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.
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
Institutions: Sun Yat-sen University, Shanghai Jiao Tong University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: G1199387736, G1230369380, G129279626, G1384485239, G1409404486, G1705254569, G1756711678, G200295169, G2173826355, G2219306473, G2351040466, G2451347695, G2532281964, G3363135377, G341529634, G350344612, G3671422335, G3681015242, G3695585404, G4272320122, G4831454592, G5481917586, G5546742448, G6068976222, G6136228938, G622470945, G6236740785, G6272091071, G6332186667, G6513902674, G6878361198, G6940241815, G7273942246, G7520252952, G7550065150, G7576208016, G778672784, G8225817820, G8548298599, G8720075954
OpenAlex ID: W4408798112