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Discovering BIX02189 as a novel anti-influenza virus compound using transcriptome signature reversion strategy
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You WU1, 2, Shu-bing CHEN1, 2, Ke TANG1, 2, Ying GUO1, 2, *
Acta Pharmaceutica Sinica | 2022, 57(10) : 3002 - 3010
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Acta Pharmaceutica Sinica | 2022, 57(10): 3002-3010
• Special Reports Ⅰ: New Targets, New Strategies for Drug Discovery and Advances in Antiviral Drug Research •
Discovering BIX02189 as a novel anti-influenza virus compound using transcriptome signature reversion strategy
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You WU1, 2, Shu-bing CHEN1, 2, Ke TANG1, 2, Ying GUO1, 2, *
Affiliations
  • 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
  • 2. 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
Published: 2022-10-12 doi: 10.16438/j.0513-4870.2022-0087
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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.

influenza virus  /  host factor  /  the transcriptomic signature of compound-perturbed cells  /  transcriptome signature reversion  /  BIX02189
You WU, Shu-bing CHEN, Ke TANG, Ying GUO. Discovering BIX02189 as a novel anti-influenza virus compound using transcriptome signature reversion strategy[J]. Acta Pharmaceutica Sinica, 2022 , 57 (10) : 3002 -3010 . DOI: 10.16438/j.0513-4870.2022-0087
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doi: 10.16438/j.0513-4870.2022-0087
  • Receive Date：2022-01-18
  • Online Date：2025-12-24
  • Published：2022-10-12
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History
  • Received：2022-01-18
  • Revised：2022-05-24
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Affiliations
    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
    2. 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
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
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Genus		 种数
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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