Discovering BIX02189 as a novel anti-influenza virus compound using transcriptome signature reversion strategy
10.16438/j.0513-4870.2022-0087
- VernacularTitle:基于转录组特征基因反向匹配方法发现抗流感病毒化合物BIX02189
- Author:
You WU
1
;
Shu-bing CHEN
1
;
Ke TANG
1
;
Ying GUO
1
Author Information
1. Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
influenza virus;
host factor;
the transcriptomic signature of compound-perturbed cells;
transcriptome signature reversion;
BIX02189
- From:
Acta Pharmaceutica Sinica
2022;57(10):3002-3010
- CountryChina
- Language:Chinese
-
Abstract:
Influenza virus is an RNA virus that classified into 4 types, A, B, C, and D, where influenza A and B virus infection may cause human acute respiratory tract infection and nearly 0.3 million deaths annually. The life cycle of influenza virus infection is highly dependent on the host response, demonstrating an important strategy of developing anti-influenza agents that target the host factors. This research utilized a transcriptome signature reversion (TSR) strategy to discover a list of multi-host-factor-target anti-influenza agents and determined their anti-influenza activities in vitro. BIX02189 was discovered and exhibited broad spectrum anti-influenza activity, with half maximal effective concentration (EC50) of 17.1 μmol·L-1 against influenza A virus H1N1 (A/Puerto Rico/8/1934) and 9.4 μmol·L-1 for influenza B virus (B/Jiangxi Xinjian/BV/39/2008). The anti-influenza A virus activity of BIX01289 is stronger than the positive control ribavirin with EC50 of 97.9 μmol·L-1 for influenza A virus H1N1 (A/Puerto Rico/8/1934). According to the unsupervised transcriptomic profile similarity clustering analysis, BIX02189 was considered to inhibit viral protein synthesis and release of influenza virus mainly through inhibiting the Raf/MEK/ERK cascade, revealing its potential mechanism of inhibiting influenza virus infection.
