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Identification of Small Molecules that Interfere with H1N1 Influenza A Viral Replication
Author(s) -
Bottini Angel,
De Surya K.,
Baaten Bas J. G.,
Wu Bainan,
Barile Elisa,
Soonthornvacharin Stephen,
Stebbins John L.,
Bradley Linda M.,
Chanda Sumit K.,
Pellecchia Maurizio
Publication year - 2012
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201200453
Subject(s) - viral replication , influenza a virus , virology , oseltamivir , biology , virus , in vivo , replication (statistics) , chemistry , computational biology , medicine , genetics , covid-19 , infectious disease (medical specialty) , disease , pathology
Successful replication of the influenza A virus requires both viral proteins and host cellular factors. In this study we used a cellular assay to screen for small molecules capable of interfering with any of such necessary viral or cellular components. We used an established reporter assay to assess influenza viral replication by monitoring the activity of co‐expressed luciferase. We screened a diverse chemical compound library, resulting in the identification of compound 7 , which inhibits a novel yet elusive target. Quantitative real‐time PCR studies confirmed the dose‐dependent inhibitory activity of compound 7 in a viral replication assay. Furthermore, we showed that compound 7 is effective in rescuing high‐dose influenza infection in an in vivo mouse model. As oseltamivir‐resistant influenza strains emerge, compound 7 could be further investigated as a new and potentially suitable scaffold for the development of anti‐influenza agents that act on novel targets.