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.
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 pan class="Species">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.
Authors: Renate König; Silke Stertz; Yingyao Zhou; Atsushi Inoue; H-Heinrich Hoffmann; Suchita Bhattacharyya; Judith G Alamares; Donna M Tscherne; Mila B Ortigoza; Yuhong Liang; Qinshan Gao; Shane E Andrews; Sourav Bandyopadhyay; Paul De Jesus; Buu P Tu; Lars Pache; Crystal Shih; Anthony Orth; Ghislain Bonamy; Loren Miraglia; Trey Ideker; Adolfo García-Sastre; John A T Young; Peter Palese; Megan L Shaw; Sumit K Chanda Journal: Nature Date: 2010-02-11 Impact factor: 49.962
Authors: J McKimm-Breschkin; T Trivedi; A Hampson; A Hay; A Klimov; M Tashiro; F Hayden; M Zambon Journal: Antimicrob Agents Chemother Date: 2003-07 Impact factor: 5.191
Authors: Linda M Bradley; Mia F Douglass; Dhrubamitra Chatterjee; Shizuo Akira; Bas J G Baaten Journal: PLoS Pathog Date: 2012-04-05 Impact factor: 6.823
Authors: Nicole N Haese; Nicholas A May; Sharon Taft-Benz; Omar Moukha-Chafiq; Nikhil Madadi; Sixue Zhang; Shuklendu D Karyakarte; Kevin J Rodzinak; Theresa H Nguyen; Michael Denton; Aaron D Streblow; Nichole A Towers; Lynn Rasmussen; Robert J Bostwick; Joseph A Maddry; Subramaniam Ananthan; Corinne E Augelli-Szafran; Mark J Suto; Wes Sanders; Nathaniel Moorman; Victor DeFilippis; Mark T Heise; Ashish K Pathak; Daniel N Streblow; Thomas E Morrison Journal: Antimicrob Agents Chemother Date: 2021-08-17 Impact factor: 5.191